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	<title>Creative Biolabs Vaccine Blog</title>
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		<title>Cell: Monkeypox mRNA Vax Packs a Bigger Punch</title>
		<link>https://www.creative-biolabs.com/blog/vaccine/cell-monkeypox-mrna-vax-packs-a-bigger-punch/</link>
		
		<dc:creator><![CDATA[biovaccine]]></dc:creator>
		<pubDate>Thu, 12 Sep 2024 03:00:39 +0000</pubDate>
				<category><![CDATA[Vaccine News]]></category>
		<category><![CDATA[Vaccine Research]]></category>
		<category><![CDATA[Monkeypox Virus]]></category>
		<category><![CDATA[Monkeypox Virus Vaccine]]></category>
		<category><![CDATA[mRNA Vaccines]]></category>
		<guid isPermaLink="false">https://www.creative-biolabs.com/blog/vaccine/?p=607</guid>

					<description><![CDATA[Researchers from the U.S. Army Medical Research Institute of Infectious Diseases and Moderna published a research paper titled &#8220;Comparison of protection against mpox following mRNA or modified vaccinia Ankara vaccination in nonhuman<a class="moretag" href="https://www.creative-biolabs.com/blog/vaccine/cell-monkeypox-mrna-vax-packs-a-bigger-punch/">Read More...</a>]]></description>
										<content:encoded><![CDATA[<p><span style="font-size: 15px;">Researchers from the U.S. Army Medical Research Institute of Infectious Diseases and Moderna published a research paper titled &#8220;Comparison of protection against mpox following mRNA or modified vaccinia Ankara vaccination in nonhuman primates&#8221; in the top international academic journal <em>Cell</em>.</span></p>
<p><span style="font-size: 15px;">The study compared the effectiveness of the MVA vaccine and the mRNA-1769 vaccine in non-human primates. The results showed that, similar to MVA, mRNA-1769 produced protection against monkeypox virus challenge and further reduced symptoms and disease course. Compared with MVA, mRNA-1769 enhanced viral control and disease reduction, highlighting the potential of mRNA vaccines to mitigate the threat of future pandemics.</span></p>
<p><span style="font-size: 15px;">Alec Freyn, a virology researcher at Moderna, said the study is the first to directly compare an investigational mRNA monkeypox vaccine with the current standard vaccine in a non-human primate model. When these vaccines are used directly in primates, we see positive effects of the <span style="color: #0000ff;"><strong><a style="color: #0000ff;" href="/vaccine/mrna-vaccine-platform.htm">mRNA vaccines</a></strong></span>, not only improving survival rates, but also reducing lesions and shortening the duration of the disease.</span></p>
<p><span style="font-size: 15px;">The MVA vaccine, originally developed to fight smallpox, contains an intact virus that has been weakened so it cannot cause disease in humans. However, this weakening also means that the MVA vaccine offers limited protection compared with other vaccines, such as the potent but potentially infectious ACAM2000. In contrast, using mRNA technology allows vaccines to include only the parts of the virus most likely to elicit a durable, protective immune response, without exposing people to the entire infectious virus. In this case, the monkeypox mRNA vaccine under study is composed of four viral antigens that are critical for the virus to attach to and enter host cells.</span></p>
<p><span style="font-size: 15px;">Galit Alter, corresponding author of the paper and virologist and immunologist at Moderna, said that with the mRNA vaccine, we can select the virus fragments that can produce the most effective immune response. This way, you can pinpoint your virus protection circle instead of being distracted by all the viruses.</span></p>
<p><span style="font-size: 15px;">Although there are studies showing that mRNA vaccines can prevent infection in non-human primates, their ability to limit disease severity has not been tested before. To directly compare the mRNA and MVA vaccines, the researchers vaccinated macaque monkeys and then exposed them to a deadly strain of monkeypox virus eight weeks after the initial vaccination. They also exposed six unvaccinated animals to the virus as a control group. After infection, the researchers monitored the animals&#8217; health for four weeks and collected blood samples to check their immune responses.</span></p>
<p><span style="font-size: 15px;">Regardless of which vaccine was used, all 12 vaccinated animals survived, while five of the six unvaccinated animals succumbed to the disease. While both vaccines reduced disease severity compared with the control group, animals vaccinated with the mRNA vaccine lost less weight and had fewer lesions than animals vaccinated with the MVA vaccine—on average, the animals in the control group had a maximum of 1448 lesions, MVA-vaccinated animals had a maximum of 607 lesions, and mRNA-vaccinated animals had a maximum of 54 lesions. The mRNA vaccine also reduced disease duration (the number of days animals develop lesions) by more than 10 days compared with the MVA vaccine and resulted in lower viral loads in blood and throat swabs, suggesting that the mRNA vaccine may also have a role in reducing transmission. More effective.</span></p>
<p><span style="font-size: 15px;">Jay Hooper, corresponding author of the paper and a virologist at the U.S. Army Medical Research Institute of Infectious Diseases, said that with mRNA technology, we can produce a vaccine that can produce a fairly effective response and has a very good safety profile. We have been working hard to develop a vaccine that prevents the spread of the virus, like the ACAM2000 vaccine, but without the safety issues. Our research suggests that mRNA technology may fill this gap.</span></p>
<p><span style="font-size: 15px;">When the researchers compared the immune responses elicited by the mRNA vaccine and the MVA vaccine, they found that the mRNA vaccine produced higher numbers of antibodies with more diverse immune functions. The study also identified different types of antibodies that were associated with enhanced viral control and fewer lesions.</span></p>
<p><span style="font-size: 15px;">The mRNA vaccine has also shown the potential to induce cross-immunity to other poxviruses, whereas the MVA vaccine generates a smaller immune response and is less potent in neutralizing distantly related poxviruses.</span></p>
<p><span style="font-size: 15px;"><img decoding="async" fetchpriority="high" class="aligncenter wp-image-608" src="https://www.creative-biolabs.com/blog/vaccine/wp-content/uploads/2024/09/vblog-202409.jpg" alt="" width="357" height="357" srcset="https://www.creative-biolabs.com/blog/vaccine/wp-content/uploads/2024/09/vblog-202409.jpg 996w, https://www.creative-biolabs.com/blog/vaccine/wp-content/uploads/2024/09/vblog-202409-300x300.jpg 300w, https://www.creative-biolabs.com/blog/vaccine/wp-content/uploads/2024/09/vblog-202409-150x150.jpg 150w, https://www.creative-biolabs.com/blog/vaccine/wp-content/uploads/2024/09/vblog-202409-768x768.jpg 768w" sizes="(max-width: 357px) 100vw, 357px" /></span></p>
<p style="text-align: center;"><span style="font-size: 12px;">Fig. 1 The mechanism diagram of monkeypox vaccine in animal models.<sup>1</sup></span></p>
<p><span style="font-size: 15px;">Alec Freyn said, &#8220;We tested the serum of monkeys that had been vaccinated with this vaccine, and these monkeys were basically resistant to all the poxviruses that we could come into contact with.&#8221; It neutralizes not only monkeypox, but also viruses such as cowpox, rabbitpox, camelpox and sheeppox. We believe this <span style="color: #0000ff;"><strong><a style="color: #0000ff;" href="/vaccine/monkeypox-virus-vaccine.htm">monkeypox virus vaccine</a></strong></span> will protect against other poxvirus threats that may arise in the future.</span></p>
<p><span style="font-size: 15px;">It is reported that Moderna&#8217;s mRNA-1769 vaccine is currently being evaluated in a Phase 1/2 clinical trial (NCT05995275) to determine the safety, tolerability and immune response of a range of doses of the mRNA-1769 vaccine in humans.</span></p>
<p><span style="font-size: 15px;">Conduct better research using our <span style="color: #0000ff;"><strong><a style="color: #0000ff;" href="/vaccine/new-products-for-monkeypox-virus-mpxv.htm">monkeypox virus products</a></strong></span>:</span></p>
<p><span style="font-size: 15px;"><strong>Antibodies</strong></span></p>
<table style="border-style: solid; width: 100%; border-color: #050505;" width="100%">
<thead>
<tr>
<td style="border-style: solid; border-color: #050505;" width="23%"><span style="font-size: 15px;">CAT</span></td>
<td style="border-style: solid; border-color: #050505;" width="76%"><span style="font-size: 15px;">Product Name</span></td>
</tr>
</thead>
<tbody>
<tr>
<td style="border-style: solid; border-color: #050505;" width="23%"><span style="color: #0000ff;"><strong><span style="font-size: 15px;"><a style="color: #0000ff;" href="/vaccine/anti-monkeypox-virus-monoclonal-antibody-vacv-5c7-mouse-igg1-kappa-53702.htm">VASX-0522-SX4</a></span></strong></span></td>
<td style="border-style: solid; border-color: #050505;" width="76%"><span style="font-size: 15px;">Anti-Monkeypox Virus Monoclonal Antibody (VACV-5C7), Mouse IgG1, Kappa</span></td>
</tr>
<tr>
<td style="border-style: solid; border-color: #050505;" width="23%"><span style="color: #0000ff;"><strong><span style="font-size: 15px;"><a style="color: #0000ff;" href="/vaccine/anti-monkeypox-virus-monoclonal-antibody-vacv-5c7-human-igg1-kappa-53703.htm">VASX-0522-SX5</a></span></strong></span></td>
<td style="border-style: solid; border-color: #050505;" width="76%"><span style="font-size: 15px;">Anti-Monkeypox Virus Monoclonal Antibody (VACV-5C7), Human IgG1, Kappa</span></td>
</tr>
<tr>
<td style="border-style: solid; border-color: #050505;" width="23%"><span style="color: #0000ff;"><strong><span style="font-size: 15px;"><a style="color: #0000ff;" href="/vaccine/anti-monkeypox-virus-monoclonal-antibody-vacv-5c7-human-igg1-fc-silent-kappa-53704.htm">VASX-0522-SX6</a></span></strong></span></td>
<td style="border-style: solid; border-color: #050505;" width="76%"><span style="font-size: 15px;">Anti-Monkeypox Virus Monoclonal Antibody (VACV-5C7), Human IgG1, Fc Silent, Kappa</span></td>
</tr>
<tr>
<td style="border-style: solid; border-color: #050505;" width="23%"><span style="color: #0000ff;"><strong><span style="font-size: 15px;"><a style="color: #0000ff;" href="/vaccine/anti-monkeypox-virus-monoclonal-antibody-vacv-5c7-human-igm-kappa-53705.htm">VASX-0522-SX7</a></span></strong></span></td>
<td style="border-style: solid; border-color: #050505;" width="76%"><span style="font-size: 15px;">Anti-Monkeypox Virus Monoclonal Antibody (VACV-5C7), Human IgM, Kappa</span></td>
</tr>
<tr>
<td style="border-style: solid; border-color: #050505;" width="23%"><span style="color: #0000ff;"><strong><span style="font-size: 15px;"><a style="color: #0000ff;" href="/vaccine/anti-monkeypox-virus-monoclonal-antibody-vacv-5c7-rabbit-igg-kappa-53706.htm">VASX-0522-SX8</a></span></strong></span></td>
<td style="border-style: solid; border-color: #050505;" width="76%"><span style="font-size: 15px;">Anti-Monkeypox Virus Monoclonal Antibody (VACV-5C7), Rabbit IgG, Kappa</span></td>
</tr>
<tr>
<td style="border-style: solid; border-color: #050505;" width="23%"><span style="color: #0000ff;"><strong><span style="font-size: 15px;"><a style="color: #0000ff;" href="/vaccine/anti-monkeypox-virus-vaccinia-a13-monoclonal-antibody-11f7-rabbit-igg-kappa-53707.htm">VASX-0522-SX9</a></span></strong></span></td>
<td style="border-style: solid; border-color: #050505;" width="76%"><span style="font-size: 15px;">Anti-Monkeypox Virus &amp; Vaccinia A13 Monoclonal Antibody (11F7), Rabbit IgG, Kappa</span></td>
</tr>
</tbody>
</table>
<p><span style="font-size: 15px;"><strong>Recombinant Protein</strong></span></p>
<table style="border-style: solid; width: 88.419%; border-color: #050505; height: 222px;" width="529">
<thead>
<tr style="height: 54px;">
<td style="height: 54px; border-style: solid; border-color: #050505;" width="160"><span style="font-size: 15px;">CAT</span></td>
<td style="height: 54px; border-style: solid; border-color: #050505;" width="369"><span style="font-size: 15px;">Product Name</span></td>
</tr>
</thead>
<tbody>
<tr style="height: 84px;">
<td style="height: 84px; border-style: solid; border-color: #050505;"><span style="color: #0000ff;"><strong><span style="font-size: 15px;"><a style="color: #0000ff;" href="/vaccine/recombinant-monkeypox-l1r-protein-aa-1-152-his-53720.htm">VASX-0622-SX1</a></span></strong></span></td>
<td style="height: 84px; border-style: solid; border-color: #050505;" width="369"><span style="font-size: 15px;">Recombinant Monkeypox L1R Protein (aa 1-152) [His]</span></td>
</tr>
<tr style="height: 84px;">
<td style="height: 84px; border-style: solid; border-color: #050505;"><span style="color: #0000ff;"><strong><span style="font-size: 15px;"><a style="color: #0000ff;" href="/vaccine/recombinant-monkeypox-a29-protein-aa-21-110-his-53721.htm">VASX-0622-SX2</a></span></strong></span></td>
<td style="height: 84px; border-style: solid; border-color: #050505;" width="369"><span style="font-size: 15px;">Recombinant Monkeypox A29 Protein (aa 21-110) [His]</span></td>
</tr>
</tbody>
</table>
<p><span style="font-size: 15px;"><strong>Detection Kits</strong></span></p>
<table style="border-style: solid; width: 77.346%; border-color: #050505; height: 247px;" width="463">
<thead>
<tr style="height: 54px;">
<td style="border-style: solid; border-color: #050505; height: 54px;" width="160"><span style="font-size: 15px;">CAT</span></td>
<td style="border-style: solid; border-color: #050505; height: 54px;" width="302"><span style="font-size: 15px;">Product Name</span></td>
</tr>
</thead>
<tbody>
<tr style="height: 84px;">
<td style="border-style: solid; border-color: #050505; height: 84px;"><span style="color: #0000ff;"><strong><span style="font-size: 15px;"><a style="color: #0000ff;" href="/vaccine/monkeypox-virus-real-time-pcr-kit-53717.htm">VASX-0522-SX1</a></span></strong></span></td>
<td style="border-style: solid; border-color: #050505; height: 84px;" width="302"><span style="font-size: 15px;">Monkeypox Virus (MPV) Real Time PCR Kit</span></td>
</tr>
<tr style="height: 55px;">
<td style="border-style: solid; border-color: #050505; height: 55px;"><span style="color: #0000ff;"><strong><span style="font-size: 15px;"><a style="color: #0000ff;" href="/vaccine/monkeypox-virus-mpv-elisa-kit-53718.htm">VASX-0522-SX2</a></span></strong></span></td>
<td style="border-style: solid; border-color: #050505; height: 55px;" width="302"><span style="font-size: 15px;">Monkeypox Virus (MPV) Antigen ELISA Kit</span></td>
</tr>
<tr style="height: 54px;">
<td style="border-style: solid; border-color: #050505; height: 54px;"><span style="color: #0000ff;"><strong><span style="font-size: 15px;"><a style="color: #0000ff;" href="/vaccine/monkeypox-virus-mpv-igg-elisa-kit-53719.htm">VASX-0522-SX3</a></span></strong></span></td>
<td style="border-style: solid; border-color: #050505; height: 54px;" width="302"><span style="font-size: 15px;">Monkeypox Virus (MPV) IgG ELISA Kit</span></td>
</tr>
</tbody>
</table>
<p><span style="font-size: 12px;">Reference</span></p>
<ol>
<li><span style="font-size: 12px;">Mucker, Eric M., <em>et al.</em>, &#8220;Comparison of protection against mpox following mRNA or modified vaccinia Ankara vaccination in nonhuman primates.&#8221; <em>Cell</em>(2024).</span></li>
</ol>
]]></content:encoded>
					
		
		
			</item>
		<item>
		<title>A Game-Changer Vaccine Delivery System in the Fight Against Tumor</title>
		<link>https://www.creative-biolabs.com/blog/vaccine/a-game-changer-vaccine-delivery-system-in-the-fight-against-tumor/</link>
		
		<dc:creator><![CDATA[biovaccine]]></dc:creator>
		<pubDate>Sat, 24 Aug 2024 06:19:13 +0000</pubDate>
				<category><![CDATA[Vaccine Research]]></category>
		<category><![CDATA[In Situ Vaccines]]></category>
		<category><![CDATA[PRR Agonists]]></category>
		<category><![CDATA[tumor vaccine]]></category>
		<guid isPermaLink="false">https://www.creative-biolabs.com/blog/vaccine/?p=600</guid>

					<description><![CDATA[The team of Professor Michael J. Mitchell of the University of Pennsylvania and Professor Drew Weissman, winner of the 2023 Nobel Prize in Physiology and Medicine, published a review paper titled &#8220;Enhancing<a class="moretag" href="https://www.creative-biolabs.com/blog/vaccine/a-game-changer-vaccine-delivery-system-in-the-fight-against-tumor/">Read More...</a>]]></description>
										<content:encoded><![CDATA[<p><span style="font-size: 15px;">The team of Professor Michael J. Mitchell of the University of Pennsylvania and Professor Drew Weissman, winner of the 2023 Nobel Prize in Physiology and Medicine, published a review paper titled &#8220;Enhancing <em>in situ</em> cancer vaccines using delivery technologies&#8221; in the journal <em>Nature Reviews Drug Discovery</em>.</span></p>
<p><span style="font-size: 15px;">The review starts from the cancer immune cycle and systematically summarizes solid tumor drugs and gene delivery technologies that enhance the effect of <em>in situ</em> vaccines. Starting from three dimensions: promoting the release of tumor antigens, enhancing tumor antigen processing and presentation, and overcoming the inhibitory tumor microenvironment, delivery technologies of different categories, different characteristics, and targeting different regions and cell types are summarized and analyzed. In addition, this review also systematically summarizes the research progress of tumor <em>in situ</em> vaccines based on delivery technology currently in the clinical trial stage. Finally, while affirming the development prospects of tumor <em>in situ</em> vaccines, the researchers outlined their existing clinical problems and the prospects for developing new <span style="color: #0000ff;"><strong><a style="color: #0000ff;" href="https://www.creative-biolabs.com/vaccine/category-delivery-systems-2.htm">vaccine delivery systems</a></strong></span>.</span></p>
<p><span style="font-size: 15px;"><img decoding="async" class="aligncenter size-full wp-image-601" src="https://www.creative-biolabs.com/blog/vaccine/wp-content/uploads/2024/08/vblog-202407-1.jpg" alt="" width="469" height="284" srcset="https://www.creative-biolabs.com/blog/vaccine/wp-content/uploads/2024/08/vblog-202407-1.jpg 469w, https://www.creative-biolabs.com/blog/vaccine/wp-content/uploads/2024/08/vblog-202407-1-300x182.jpg 300w" sizes="(max-width: 469px) 100vw, 469px" /></span></p>
<p style="text-align: center;"><span style="font-size: 12px;">Fig. 1 Improving <em>in situ</em> tumor vaccines using delivery technology.<sup>1</sup></span></p>
<ul>
<li><span style="font-size: 15px;">Promote tumor antigen release</span></li>
</ul>
<p><span style="font-size: 15px;">Inducing tumor cell lysis and death can release tumor antigens, but methods such as the sole use of chemotherapy drugs, physical induction, and biomolecule induction all have limitations. This article analyzes how modified delivery, delivery, and co-delivery technologies can address these issues and promote tumor antigen release through <em>in situ</em> tumor vaccines.</span></p>
<ol>
<li><span style="font-size: 15px;">Chemotherapy drug delivery technologies include PEG modification to improve tissue distribution, active targeting ligand connection to achieve targeted delivery, pH-responsive specific delivery, and local chemotherapeutic agent delivery. Such nanoparticle-mediated chemotherapeutic drug delivery is based on tumor targeting. Site-specific delivery can effectively improve drug accumulation in tumors.</span></li>
<li><span style="font-size: 15px;">Delivering nanosensitizers mainly includes designing delivery materials as sensitizers for radiation, photodynamic therapy (PDT), sonodynamic therapy (SDT), and physical therapy methods such as microwave, ultrasound, and cryoablation therapy, to solve the problem of tumors. Low cell lysis efficiency and extratumoral toxicity are associated with induction by physical methods.</span></li>
<li><span style="font-size: 15px;">The delivery of biomolecules can destroy cell membranes or regulate cell death to induce tumor cell lysis, broadening the application scope of biomacromolecules, including oncolytic viruses and cytolytic peptides.</span></li>
</ol>
<ul>
<li><span style="font-size: 15px;">Enhanced tumor antigen processing and presentation</span></li>
</ul>
<p><span style="font-size: 15px;">Antigen-presenting cell (APC)-mediated processing and presentation of <span style="color: #0000ff;"><strong><a style="color: #0000ff;" href="https://www.creative-biolabs.com/vaccine/category-antigens-1.htm">tumor antigens</a></strong></span> can be improved through activation of pattern recognition receptors (PRRs). Next, we discuss how delivery technologies can be used to improve antigen processing and presentation by dendritic cells through direct and indirect activation of PRRs.</span></p>
<p><span style="font-size: 15px;">On the one hand, agonists that deliver PRRs can be used to directly activate the innate immune response, including the delivery of synthetic <span style="color: #0000ff;"><strong><a style="color: #0000ff;" href="https://www.creative-biolabs.com/vaccine/l-prrs-agonist-for-vaccine-development-24.htm">PRR agonists</a></strong></span>, the delivery of nanoparticles of virus-derived materials or bacterial-derived materials, etc. These reagents can be recognized by PRRs, such as Toll-like receptors (TLRs), NOD-like receptors (NLRs), or cyclic GMP-AMP synthetase-interferon gene stimulator (cGAS-STING), stimulating antigen processing and presentation.</span></p>
<p><span style="font-size: 15px;">In addition, PRRs can be activated indirectly using delivery methods such as targeting immunogenic cell death (ICD) or targeting endogenous retroviral (ERV) genes. Delivery of targeted ICD activation reagents does not directly activate PRRs, but causes tumor cells to release tumor antigens and damage-associated molecular patterns (DAMPs), which can be recognized by PRRs and activate innate immune responses. Similarly, nanoparticles used to deliver epigenetic drugs (DNMTis or HDACis, etc.) can activate ERV genes in cancer cells, leading to the formation of ssRNA, dsRNA, and dsDNA, which can also trigger innate immune responses after being recognized by PRRs.</span></p>
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<tr style="height: 54px;">
<td style="width: 28.1457%; height: 54px; border-style: solid; border-color: #050505;" width="184"><span style="font-size: 15px;">VAdv-Ly0019</span></td>
<td style="width: 38.4258%; height: 54px; border-style: solid; border-color: #050505;" width="184"><span style="color: #0000ff;"><strong><span style="font-size: 15px;"><a style="color: #0000ff;" href="https://www.creative-biolabs.com/vaccine/cyclic-g-2-5-pa-3-5-p-18375.htm">Cyclic [G(2&#8242;, 5&#8242;)pA(3&#8242;, 5&#8242;)p]</a></span></strong></span></td>
<td style="width: 34.4218%; height: 54px; border-style: solid; border-color: #050505;" width="184"><span style="font-size: 15px;">PRR Agonist</span></td>
</tr>
<tr style="height: 54px;">
<td style="width: 28.1457%; height: 54px; border-style: solid; border-color: #050505;" width="184"><span style="font-size: 15px;">VAdv-Ly0020</span></td>
<td style="width: 38.4258%; height: 54px; border-style: solid; border-color: #050505;" width="184"><span style="color: #0000ff;"><strong><span style="font-size: 15px;"><a style="color: #0000ff;" href="https://www.creative-biolabs.com/vaccine/3-3-cgamp-18376.htm">3&#8217;3&#8242;-cGAMP</a></span></strong></span></td>
<td style="width: 34.4218%; height: 54px; border-style: solid; border-color: #050505;" width="184"><span style="font-size: 15px;">PRR Agonist</span></td>
</tr>
<tr style="height: 68px;">
<td style="width: 28.1457%; height: 68px; border-style: solid; border-color: #050505;" width="184"><span style="font-size: 15px;">VAdv-Ly0021</span></td>
<td style="width: 38.4258%; height: 68px; border-style: solid; border-color: #050505;" width="184"><span style="color: #0000ff;"><strong><span style="font-size: 15px;"><a style="color: #0000ff;" href="https://www.creative-biolabs.com/vaccine/cyclic-diadenylate-monophosphate-18377.htm">Cyclic Diadenylate Monophosphate</a></span></strong></span></td>
<td style="width: 34.4218%; height: 68px; border-style: solid; border-color: #050505;" width="184"><span style="font-size: 15px;">PRR Agonist</span></td>
</tr>
</tbody>
</table>
<h6><span style="font-size: 15px;">Delivery technologies to improve tumor antigen processing and presentation</span></h6>
<ul>
<li><span style="font-size: 15px;">Overcoming the immunosuppressive tumor microenvironment</span></li>
</ul>
<p><span style="font-size: 15px;">Solid tumors have a highly immunosuppressive tumor microenvironment (TME). This review discusses how delivery technologies targeting immune checkpoints, cytokines, and suppressive immune cells in the suppressive TME can be used to improve <em>in situ</em> tumor vaccines.</span></p>
<ol>
<li><span style="font-size: 15px;">Target immune checkpoints. For example, local delivery of immune checkpoint inhibitors that synergize with <em>in situ</em> vaccines and target the CD47-SIRPa axis can improve vaccine efficacy and reduce adverse effects caused by systemic immune checkpoint blockade through local delivery and stimulus-responsive delivery technology. Reactions are minimized.</span></li>
<li><span style="font-size: 15px;">Immunomodulation by local delivery of cytokines. This method includes direct delivery of cytokines (IL-2, IL-12, IL-15, etc.) or delivery of nanoparticles encoding various cytokine mRNAs. Compared with traditional cytokine administration routes (such as intravenous injection ), this method can improve efficacy and reduce systemic toxicity, improving the effect of <em>in situ</em> tumor vaccines.</span></li>
<li><span style="font-size: 15px;">Regulate suppressive immune cells. The tumor microenvironment can cause the accumulation of immunosuppressive cells such as Treg cells, myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages (TAMs). Designing delivery systems that deliver small molecules to deplete suppressive immune cells or deliver therapeutic RNA to remodel immune suppressive cells can enhance the efficacy of <em>in situ</em> tumor vaccines.</span></li>
<li><span style="font-size: 15px;">Target metabolism. For example, injecting compounds that regulate metabolism into tumors is intended to enhance anti -tumor immunity by manipulating the metabolism of cancer cells and immune cells that infiltrate tumors.</span></li>
</ol>
<p><span style="font-size: 15px;"> <img decoding="async" class="aligncenter size-full wp-image-602" src="https://www.creative-biolabs.com/blog/vaccine/wp-content/uploads/2024/08/vblog-202407-2.jpg" alt="" width="381" height="373" srcset="https://www.creative-biolabs.com/blog/vaccine/wp-content/uploads/2024/08/vblog-202407-2.jpg 381w, https://www.creative-biolabs.com/blog/vaccine/wp-content/uploads/2024/08/vblog-202407-2-300x294.jpg 300w" sizes="(max-width: 381px) 100vw, 381px" /></span></p>
<p style="text-align: center;"><span style="font-size: 12px;">Fig. 2 Delivery technologies to overcome the suppressive immune microenvironment. <sup>1</sup></span></p>
<ul>
<li><span style="font-size: 15px;">Clinical research</span></li>
</ul>
<p><span style="font-size: 15px;">This review also provides a systematic summary of <em>in situ</em> tumor vaccine delivery systems currently undergoing clinical evaluation. In order to improve the release of tumor antigens, clinical trials of INT230-6 and the radiosensitizer Hensify, alone or in combination with immune checkpoint blockade therapy, for the treatment of various types of cancer are ongoing. While drugs in clinical trials, such as Hiltonol, BO-112, G100, and CMP-001, can improve antigen processing and presentation. To overcome the suppressive immune microenvironment, clinical trials are currently underway on mRNA delivery systems encoding cytokines, including MEDI1191, mRNA-2416, mRNA-2752, and SAR44100. In summary, more and more clinical studies are ongoing to explore <em>in situ</em> tumor vaccines based on delivery technology.</span></p>
<h6><span style="font-size: 15px;">Summary and Outlook</span></h6>
<p><span style="font-size: 15px;">Tumor <em>in situ</em> vaccines have significant advantages because they can avoid the need for antigen identification and isolation and solve the problem of tumor heterogeneity. Many drugs are under clinical evaluation, and some products have been approved. They have great prospects in the treatment of solid tumors. Currently, more and more delivery technologies can be used to enhance the clinical therapeutic effect of <em>in situ</em> vaccines.</span></p>
<p><span style="font-size: 15px;">In the future, it is still expected to further develop the delivery technology of <em>in situ</em> vaccines for tumors through the following approaches: first, there is an urgent need for delivery technology that can specifically capture tumor antigens and deliver them to APC to induce specific immune responses; second, it should be based on immune The safety characteristics of modulators are focused on developing a more durable sustained-release strategy for <em>in situ</em> tumor vaccines; the third is to gradually optimize the efficacy of local immunotherapy or combination therapy and overcome the accessibility challenges of <em>in situ</em> vaccines to tumor lesions.</span></p>
<p><span style="font-size: 15px;">Taken together, with continuous improvement, these delivery systems will significantly enhance the effectiveness of existing <em>in situ</em> vaccine-based cancer treatments and create more advanced cancer immunotherapies, which are expected to have great potential in basic immunology research and clinical use of <em>in situ</em> vaccination in the future. are more widely used in the environment.</span></p>
<p><span style="font-size: 12px;">Reference</span></p>
<ol>
<li><span style="font-size: 12px;">Gong, Ningqiang, et al. &#8220;Enhancing <em>in situ</em> cancer vaccines using delivery technologies.&#8221; <em>Nature Reviews Drug Discovery</em>(2024): 1-19.</span></li>
</ol>
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		<title>New Vaccine Technology Released: Dendritic Cell-Targeting VLP as mRNA Vaccine Carriers</title>
		<link>https://www.creative-biolabs.com/blog/vaccine/new-vaccine-technology-released-dendritic-cell-targeting-vlp-as-mrna-vaccine-carriers/</link>
		
		<dc:creator><![CDATA[biovaccine]]></dc:creator>
		<pubDate>Tue, 23 Jul 2024 08:13:20 +0000</pubDate>
				<category><![CDATA[Uncategorized]]></category>
		<category><![CDATA[Dendritic Cell Vaccine]]></category>
		<category><![CDATA[LNP mRNA vaccine]]></category>
		<guid isPermaLink="false">https://www.creative-biolabs.com/blog/vaccine/?p=595</guid>

					<description><![CDATA[Recently, the journal Nature Biomedical Engineering published a research paper titled &#8220;Dendritic-cell-targeting virus-like particles as latent mRNA vaccine carriers&#8221; about a new vaccine platform technology that can specifically target dendritic cells (DCs)<a class="moretag" href="https://www.creative-biolabs.com/blog/vaccine/new-vaccine-technology-released-dendritic-cell-targeting-vlp-as-mrna-vaccine-carriers/">Read More...</a>]]></description>
										<content:encoded><![CDATA[<p><span style="font-size: 15px;">Recently, the journal <em>Nature Biomedical Engineering</em> published a research paper titled &#8220;Dendritic-cell-targeting virus-like particles as latent mRNA vaccine carriers&#8221; about a new vaccine platform technology that can specifically target dendritic cells (DCs) and efficiently deliver mRNA and protein—DC-targeted viroid vector (DVLP).</span></p>
<p><span style="font-size: 15px;">This brand-new vaccine technology can not only carry mRNA but also display the three-dimensional structure of antigenic proteins on the surface of vaccine particles. It has the ability to effectively activate humoral immunity and cellular immunity and can significantly prevent SARS-CoV-2 infections. In the simple situation that is regarded as a black hole in vaccine development, herpes virus prevention has also played a significant role, bringing potential treatment and prevention methods to hundreds of millions of HSV-infected people around the world. DVLP vaccine technology is expected to become a new vaccine platform and play an important role in the treatment and prevention of viral infections, tumors, and aging.</span></p>
<p><span style="font-size: 15px;">First, the research team conducted a proof-of-concept study on a <strong><span style="color: #0000ff;"><a style="color: #0000ff;" href="https://www.creative-biolabs.com/vaccine/viral-vector-vaccine-design.htm">virus-like vector vaccine</a></span></strong>. The research team designed multiple MS2 stem-loops on the target mRNA, allowing them to use the interaction between the MS2 stem-loop structure and the MS2 coat protein to simultaneously load the lentiviral GagPol protein into a virus-like vector, becoming part of its structure. During this process, antigens, which are membrane proteins, will be loaded together and displayed on the surface of DVLP. The researchers verified the successful implementation of this vaccine design idea through various technical means such as electron microscopy, Western blot, and confocal laser imaging.</span></p>
<p><span style="font-size: 15px;">On this basis, the research team carried out the design and verification of virus-like vectors with dendritic cell targeting. DC is the most important antigen-presenting cell and plays a key role in the effectiveness of vaccines. Currently, PROVENGE, the only approved tumor vaccine in the world, is a <strong><span style="color: #0000ff;"><a style="color: #0000ff;" href="https://www.creative-biolabs.com/vaccine/dendritic-cell-vaccines.htm">DC vaccine</a></span></strong>. However, PROVENGE production is similar to CAR-T cell therapy. The process is complex and cumbersome, involving the isolation of the patient&#8217;s own cells, preparation <em>in vitro</em>, and then infusion into the body. Therefore, it is necessary to develop vaccine technology that can target DCs <em>in vivo</em>, reduce the production success and price of DC vaccines, and improve patient accessibility.</span></p>
<p><span style="font-size: 15px;">Therefore, the research team first engineered the Sindbis virus glycoprotein SV-G and replaced the broad-spectrum affinity glycoprotein VSV-G to achieve specific targeting of DCs by virus-like vectors by recognizing the DC surface protein DC-SIGN. By tracking the infection of dendritic cell lines <em>in vitro</em> and the infection of DCs <em>in vivo</em>, the research team verified that the SV-G modified virus-like vector indeed obtained the targeting ability of DCs. The research team named this virus-like vector vaccine technology with DC-targeting DVLP. By detecting the distribution of mRNA in the body, the research team found that, compared with LNP, DVLP can efficiently deliver antigen mRNA into DCs, and DCs can migrate to lymph nodes more effectively. DVLP also activated cellular immunity more effectively than the LNP mRNA vaccine.</span></p>
<p><span style="font-size: 15px;">Finally, the research team used two viral infections, SARS-CoV-2 and HSV-1, as disease models to evaluate the protective effect of the DVLP vaccine on mice. In the SARS-CoV-2 real virus infection experiment, the research team found that mice immunized with DVLP Spike had significantly reduced viral loads in the lungs and trachea, and at the same time attenuated the pulmonary inflammatory response. In the HSV-1 skin infection model, the research team found that mice immunized with DVLP gB1-gD1 produced neutralizing antibodies that cross-protected HSV-1 and HSV-2. The viral load was significantly reduced, effectively preventing HSV infection from damaging the skin of mice.</span></p>
<p><span style="font-size: 15px;">In summary, this study developed a new vaccine technology, DVLP, that can target DCs <em>in vivo</em>, deliver mRNA and display antigenic proteins at the same time, and stimulate strong humoral and cellular immune responses. Therefore, DVLP is expected to become a new generation of vaccine technology to fight viral infections, prevent and treat tumors, and treat aging. At present, preparatory work has also been launched for anti-tumor clinical research based on this <strong><span style="color: #0000ff;"><a style="color: #0000ff;" href="https://www.creative-biolabs.com/vaccine/vaccine-technology.htm">vaccine technology</a></span></strong>.</span></p>
<p><span style="font-size: 15px;">mRNA Vaccine Services at Creative Biolabs</span></p>
<ul>
<li><span style="color: #0000ff; font-size: 15px;"><strong><a style="color: #0000ff;" href="https://www.creative-biolabs.com/vaccine/non-replicating-mrna-vaccine-platform.htm">Non-replicating mRNA Vaccine</a></strong></span></li>
<li><span style="color: #0000ff; font-size: 15px;"><strong><a style="color: #0000ff;" href="https://www.creative-biolabs.com/vaccine/self-amplifying-mrna-sam-vaccine-platform.htm">Self-Amplifying RNA Vaccine</a></strong></span></li>
</ul>
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		<title>Cell: Groundbreaking Personalized mRNA Vaccine Targets Glioblastoma</title>
		<link>https://www.creative-biolabs.com/blog/vaccine/cell-groundbreaking-personalized-mrna-vaccine-targets-glioblastoma/</link>
		
		<dc:creator><![CDATA[biovaccine]]></dc:creator>
		<pubDate>Fri, 21 Jun 2024 03:07:59 +0000</pubDate>
				<category><![CDATA[Vaccine Research]]></category>
		<category><![CDATA[Glioblastoma Vaccine]]></category>
		<category><![CDATA[mRNA Vaccine]]></category>
		<guid isPermaLink="false">https://www.creative-biolabs.com/blog/vaccine/?p=590</guid>

					<description><![CDATA[In a first-of-its-kind human clinical trial involving four adult patients, an mRNA cancer vaccine developed by the University of Florida rapidly reprograms the immune system to attack glioblastoma, the most aggressive and<a class="moretag" href="https://www.creative-biolabs.com/blog/vaccine/cell-groundbreaking-personalized-mrna-vaccine-targets-glioblastoma/">Read More...</a>]]></description>
										<content:encoded><![CDATA[<p><span style="font-size: 15px;">In a first-of-its-kind human clinical trial involving four adult patients, an mRNA cancer vaccine developed by the University of Florida rapidly reprograms the immune system to attack glioblastoma, the most aggressive and deadly brain tumor.</span></p>
<p><span style="font-size: 15px;">These results reflect the treatment outcomes of 10 pet dogs with naturally occurring brain tumors, whose owners agreed to participate in the treatment as they had no other options, as well as the results of a preclinical mouse model. This breakthrough will now be tested in a pediatric phase 1 clinical trial for the treatment of brain cancer. The findings were published in the May 9, 2024, issue of the journal Cell, titled &#8220;RNA aggregates harness the danger response for potent cancer immunotherapy&#8221;.</span></p>
<p><span style="font-size: 15px;">This discovery represents a potential new approach to recruit the immune system against the notoriously treatment-resistant cancer using mRNA technology and iterations of lipid nanoparticles, similar to the COVID-19 vaccine. However, it has two key differences: the use of the patient&#8217;s own tumor cells to construct a personalized vaccine and a newly designed complex delivery mechanism.</span></p>
<p><span style="font-size: 15px;">Elias Sayour, the corresponding author of the paper and a pediatric oncologist at the University of Florida, said, &#8220;Instead of a single type of particle, we&#8217;re injecting clusters of particles wrapped together like an onion, like a bag of onions. We are able to do this in the context of cancer because these clusters of particles alert the immune system in a much more profound way than a single particle.&#8221; Like other immunotherapies, this newly developed vaccine attempts to &#8220;educate&#8221; the immune system to recognize the tumor as foreign.</span></p>
<p><span style="font-size: 15px;">One of the most impressive findings, Sayour says, is that the new vaccine, given intravenously, quickly provokes a strong response from the immune system that rejects the tumor. &#8220;In less than 48 hours, we can see these tumors go from what we call &#8216;cold&#8217; tumors — immune cold, very few immune cells, very silent immune response — to &#8216;hot&#8217; tumors, with a very active immune response,&#8221; he said. &#8220;It&#8217;s very surprising given how quickly this is happening, and it tells us that we are able to activate the early parts of the immune system very quickly to fight these cancers, which is critical for unlocking the late effects of the immune response.&#8221;</span></p>
<p><span style="font-size: 15px;">Glioblastoma is one of the most devastating cancers, with a median survival of about 15 months. The current standard of care includes surgery, radiotherapy, and some combination of chemotherapy.</span></p>
<p><span style="font-size: 15px;">The newly published paper is the culmination of promising translational results from seven years of research by the authors, who began with a preclinical mouse model and then experimented with 10 pet dogs with spontaneous advanced brain cancer, who had no other treatment options.</span></p>
<p><span style="font-size: 15px;">This experiment on pet dogs was conducted with the consent of the owner. Dr. Sheila Carrera-Justiz, a veterinary neuroscientist at the University of Florida College of Veterinary Medicine, said dogs provide a naturally occurring model for malignant gliomas because they are the only species with a high incidence of spontaneous brain tumors. She noted that gliomas in dogs are generally terminally ill.</span></p>
<p><span style="font-size: 15px;">After treating pet dogs with spontaneous brain cancer with a <span style="color: #0000ff;"><strong><a style="color: #0000ff;" href="/vaccine/mrna-vaccine-platform.htm">personalized mRNA vaccine</a></strong></span>, Sayour&#8217;s team advanced their research into a small, clinical trial to ensure safety and test feasibility before scaling up to a larger clinical trial.</span></p>
<p><span style="font-size: 15px;"><img decoding="async" loading="lazy" class="aligncenter wp-image-591" src="https://www.creative-biolabs.com/blog/vaccine/wp-content/uploads/2024/06/vblog-202406-1.jpg" alt="" width="268" height="268" srcset="https://www.creative-biolabs.com/blog/vaccine/wp-content/uploads/2024/06/vblog-202406-1.jpg 375w, https://www.creative-biolabs.com/blog/vaccine/wp-content/uploads/2024/06/vblog-202406-1-300x300.jpg 300w, https://www.creative-biolabs.com/blog/vaccine/wp-content/uploads/2024/06/vblog-202406-1-150x150.jpg 150w" sizes="(max-width: 268px) 100vw, 268px" /></span></p>
<p style="text-align: center;"><span style="font-size: 12px;">Fig.1 mRNA Vaccine for Cancer Therapy.<sup>1</sup></span></p>
<p><span style="font-size: 15px;">In a cohort of four patients, genetic material called mRNA was extracted from each patient&#8217;s own surgically removed brain tumor. This mRNA was then amplified and wrapped in a high-tech package of newly designed biocompatible lipid nanoparticles. These nanoparticles made the tumor cells &#8220;look&#8221; like a dangerous virus when reinjected into the bloodstream, eliciting a response from the immune system. This personalized mRNA vaccine is individually designed for each patient with the goal of maximizing the use of their unique immune system.</span></p>
<p><span style="font-size: 15px;">&#8220;Making mRNA cancer vaccines in this way can produce similar and strong responses in mice, pet dogs that spontaneously develop cancer, and human brain cancer patients,&#8221; said Duane Mitchell, co-author of the paper and director of the Institute for Clinical and Translational Science at the University of Florida. &#8220;This is a very important finding because we often don&#8217;t know if preclinical studies in animals translate into similar responses in patients. mRNA vaccines and therapeutics have undoubtedly been a hot topic since the COVID-19 pandemic, but this is a novel and unique way of delivering mRNA that can generate these really significant and rapid immune responses that we see in animals and humans.&#8221;</span></p>
<p><span style="font-size: 15px;">While it is too early to evaluate the clinical efficacy of this personalized mRNA vaccine in the early stages of this clinical trial, the disease-free survival of these four patients was longer than expected. In addition, the median survival of the ten pet dogs after receiving this personalized mRNA vaccine injection was 139 days, compared to the typical 30 to 60 days for dogs with this disease.</span></p>
<p><span style="font-size: 15px;">As a next step, the authors will expand the Phase 1 clinical trial to include up to 24 adult and pediatric patients to validate their findings. Once the optimal safe dose is confirmed, an estimated 25 children will be enrolled in the Phase 2 clinical trial.</span></p>
<p><span style="font-size: 15px;">Despite the encouraging results, the authors acknowledge that there is still uncertainty about how best to use the immune system while minimizing potential adverse side effects. &#8220;I hope this could be a new paradigm for us to treat patients, a new platform technology for us to modulate the immune system.&#8221;</span></p>
<p><span style="font-size: 15px;">Creative Biolabs is a leader in the field of cancer vaccines. We provide development services for different types of cancer vaccines, including:</span></p>
<table style="border-style: solid; border-color: #050505;">
<tbody>
<tr>
<td style="border-style: solid; border-color: #050505; text-align: center;" width="160">
<p style="text-align: center;"><span style="color: #0000ff;"><strong><span style="font-size: 15px;"><a style="color: #0000ff;" href="/vaccine/cutaneous-tumors.htm">Cutaneous Tumors</a></span></strong></span></p>
</td>
<td style="border-style: solid; border-color: #050505; text-align: center;" width="180"><span style="color: #0000ff;"><strong><span style="font-size: 15px;"><a style="color: #0000ff;" href="/vaccine/genitourinary-malignancies.htm">Genitourinary Malignancies</a></span></strong></span></td>
<td style="border-style: solid; border-color: #050505; text-align: center;" width="208"><span style="color: #0000ff;"><strong><span style="font-size: 15px;"><a style="color: #0000ff;" href="/vaccine/gynecologic-malignancies.htm">Gynecologic Malignancies</a></span></strong></span></td>
</tr>
<tr>
<td style="border-style: solid; border-color: #050505; text-align: center;" width="160"><span style="color: #0000ff;"><strong><span style="font-size: 15px;"><a style="color: #0000ff;" href="/vaccine/lung-cancer-vaccines.htm">Lung Cancer Vaccine</a></span></strong></span></td>
<td style="border-style: solid; border-color: #050505; text-align: center;" width="180"><span style="color: #0000ff;"><strong><span style="font-size: 15px;"><a style="color: #0000ff;" href="/vaccine/head-and-neck-cancers.htm">Head and Neck Cancers</a></span></strong></span></td>
<td style="border-style: solid; border-color: #050505; text-align: center;" width="208"><span style="color: #0000ff;"><strong><span style="font-size: 15px;"><a style="color: #0000ff;" href="/vaccine/hematologic-malignancies.htm">Hematologic Malignancies Vaccine</a></span></strong></span></td>
</tr>
<tr>
<td style="border-style: solid; border-color: #050505; text-align: center;" width="160"><span style="color: #0000ff;"><strong><span style="font-size: 15px;"><a style="color: #0000ff;" href="/vaccine/pediatric-cancer.htm">Pediatric Cancer</a></span></strong></span></td>
<td style="border-style: solid; border-color: #050505; text-align: center;" width="180"><span style="color: #0000ff;"><strong><span style="font-size: 15px;"><a style="color: #0000ff;" href="/vaccine/neuroendocrine-tumors.htm">Neuroendocrine Tumors</a></span></strong></span></td>
<td style="border-style: solid; border-color: #050505; text-align: center;" width="208"><span style="color: #0000ff;"><strong><span style="font-size: 15px;"><a style="color: #0000ff;" href="/vaccine/thyroid-cancer-vaccines.htm">Thyroid Cancer Vaccine</a></span></strong></span></td>
</tr>
<tr>
<td style="border-style: solid; border-color: #050505; text-align: center;" width="160"><span style="color: #0000ff;"><strong><span style="font-size: 15px;"><a style="color: #0000ff;" href="/vaccine/gastrointestinal-cancers.htm">Gastrointestinal Cancers Vaccine</a></span></strong></span></td>
<td style="border-style: solid; border-color: #050505; text-align: center;" width="180"><span style="color: #0000ff;"><strong><span style="font-size: 15px;"><a style="color: #0000ff;" href="/vaccine/brain-tumor-vaccines.htm">Brain Tumor</a></span></strong></span></td>
<td style="border-style: solid; border-color: #050505; text-align: center;" width="208"><span style="color: #0000ff;"><strong><span style="font-size: 15px;"><a style="color: #0000ff;" href="/vaccine/sarcomas-vaccines.htm">Sarcomas Vaccine</a></span></strong></span></td>
</tr>
</tbody>
</table>
<p><span style="font-size: 12px;">Reference</span></p>
<ol>
<li><span style="font-size: 12px;">Mendez-Gomez, Hector R., et al. &#8220;RNA aggregates harness the danger response for potent cancer immunotherapy.&#8221; <em>Cell</em>10 (2024): 2521-2535.</span></li>
</ol>
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		<title>New Progress! DNA Cancer Antigen Vaccine to Treat Hepatocellular Carcinoma</title>
		<link>https://www.creative-biolabs.com/blog/vaccine/new-progress-dna-cancer-antigen-vaccine-to-treat-hepatocellular-carcinoma/</link>
		
		<dc:creator><![CDATA[biovaccine]]></dc:creator>
		<pubDate>Tue, 14 May 2024 09:02:33 +0000</pubDate>
				<category><![CDATA[Vaccine Research]]></category>
		<category><![CDATA[cancer vaccine]]></category>
		<guid isPermaLink="false">https://www.creative-biolabs.com/blog/vaccine/?p=585</guid>

					<description><![CDATA[Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer and the leading cause of cancer-related deaths worldwide. Despite advances in the treatment of advanced hepatocellular carcinoma in recent years,<a class="moretag" href="https://www.creative-biolabs.com/blog/vaccine/new-progress-dna-cancer-antigen-vaccine-to-treat-hepatocellular-carcinoma/">Read More...</a>]]></description>
										<content:encoded><![CDATA[<p><span style="font-size: 15px;">Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer and the leading cause of cancer-related deaths worldwide. Despite advances in the treatment of advanced hepatocellular carcinoma in recent years, its 5-year survival rate is still less than 10%. Advanced hepatocellular carcinoma is a relatively immunotolerant tumor type that typically presents with low T cell infiltration and moderate tumor mutational burden. The response rate of immune checkpoint inhibitors (ICIs) targeting PD-1 as monotherapy is approximately 12% to 18%.</span></p>
<p><span style="font-size: 15px;">Mutations in the tumor genome cause tumors to express abnormal proteins that are not normally present in normal cell pools, also known as tumor neoantigens. Advances in next-generation sequencing technology have led to the development of personalized immunotherapies for individual cancer patients. Patients with innate immunity to tumor neoantigens often respond strongly to immune checkpoint inhibitors, which provides an initial rationale for combining immune checkpoint inhibitors with therapies that induce neoantigen-specific immunity.</span></p>
<p><span style="font-size: 15px;">On April 7, 2024, researchers from Geneos Therapeutics and Johns Hopkins University published a research paper entitled &#8220;Personalized neoantigen vaccine and pembrolizumab in advanced hepatocellular carcinoma: a phase 1 and 2 trial&#8221; in the journal <em>Nature Medicine</em>.</span></p>
<p><span style="font-size: 15px;">Results from the Phase 1/2 clinical trial of the personalized therapeutic cancer vaccine GNOS-PV02 (coded by plasmids for up to 40 tumor neoantigens) in combination with pembrolizumab (an anti-PD-1 monoclonal antibody) in advanced hepatocellular carcinoma showed an objective response rate of 30.6% (11/36 patients) in 36 patients with advanced hepatocellular carcinoma who had previously received too much tyrosine kinase inhibitor (mTKI), including 3 patients with complete response and 8 patients with partial response.</span></p>
<p><span style="font-size: 15px;">The objective response rate of 30.6% was nearly twice that of pembrolizumab alone (16.9%), demonstrating that <strong><span style="color: #0000ff;"><a style="color: #0000ff;" href="/vaccine/personalized-neoantigen-cancer-vaccine.htm">personalized cancer vaccines</a></span></strong> can enhance the clinical response to anti-PD-1 therapy in patients with advanced hepatocellular carcinoma.</span></p>
<p><span style="font-size: 15px;">In preclinical studies, therapeutic cancer vaccines targeting mutation-associated neoantigens induced tumor-specific T cell responses and inhibited tumor growth.</span></p>
<p><span style="font-size: 15px;">Preliminary clinical trials of personalized therapeutic cancer vaccines (PTCVs) have also demonstrated the induction of neoantigen-specific immune responses in cancer patients.</span></p>
<p><span style="font-size: 15px;">Recently, data from a Phase 2b clinical trial of Moderna&#8217;s cancer vaccine mRNA-4157 in combination with pembrolizumab (an anti-PD-1 monoclonal antibody) in advanced melanoma showed that the combination significantly improved recurrence-free survival (RFS) compared to pembrolizumab alone, with a 49% lower risk of recurrence or death and a 62% lower risk of distant metastasis or death.</span></p>
<p><span style="font-size: 15px;">However, for tumor types that respond poorly to immunotherapy, such as hepatocellular carcinoma, it has not been proven whether vaccine-induced T cells are able to enter pre-existing tumors and induce tumor clearance in combination with anti-PD-1 therapy.</span></p>
<p><span style="font-size: 15px;">In this study, the research team conducted a single-arm, open-label, multicenter Phase 1/2 clinical trial in 36 patients with advanced hepatocellular carcinoma who had previously received too much tyrosine kinase inhibitor (mTKI) to investigate the therapeutic efficacy of GNOS-PV02, a personalized therapeutic cancer vaccine, in combination with pembrolizumab (an anti-PD-1 monoclonal antibody). The primary endpoints of this clinical trial are safety and immunogenicity, and the secondary endpoints are treatment efficacy and feasibility.</span></p>
<p><span style="font-size: 15px;">This personalized therapeutic cancer vaccine, GNOS-PV02, consists of a DNA plasmid encoding up to 40 tumor neoantigens that were determined by DNA and RNA sequencing and germ cell DNA sequencing of each patient&#8217;s tumor sample. GNOS-PV02 is co-formulated with another plasmid encoding the cytokine interleukin-12 (pIL-12), which acts as a vaccine adjuvant, via intradermal injection and is facilitated by an <em>in vivo</em> electroporation device. Intradermal injection of pIL12 results only in local and transient IL-12 production at the injection site and promotes locally induced cellular responses to expressed antigens.</span></p>
<p><span style="font-size: 15px;">The most common treatment-related adverse event was injection site reactions, which were observed in 15 (41.6%) of 36 patients. No dose-limiting toxicities or treatment-related ≥ grade 3 adverse events were observed, and the objective response rate was 30.6% (11/36), of which 8.3% (3/36) patients achieved complete response.</span></p>
<p><span style="font-size: 15px;"><img decoding="async" loading="lazy" class="aligncenter  wp-image-586" src="https://www.creative-biolabs.com/blog/vaccine/wp-content/uploads/2024/05/vblog-202405-1.jpg" alt="" width="391" height="229" /></span></p>
<p style="text-align: center;"><span style="font-size: 12px;">Fig. 1 The clinical response of GNOS-PV02.<sup>1</sup></span></p>
<p><span style="font-size: 15px;">Clinical response correlates with the number of neoantigens encoded in the vaccine, and patients who receive a vaccine that encodes a larger number of neoantigens have better treatment outcomes. Further testing revealed that 19 of the 22 evaluable patients (86.4%) developed neoantigen-specific T cell responses. Multiparametric cell analysis showed that vaccine-specific CD4+ and CD8+ effector T cells were viable, proliferating, and killing. T cell receptor β chain (TCRβ) sequencing results showed clonal expansion and tumor infiltration of T cells enriched by the vaccine. Single-cell analysis shows clonal expansion of T cells with cytotoxic T cell phenotypes after treatment. Cyclability to vaccine-encoded neoantigens was confirmed by TCR-complementation-determining region cloning of expanded T cell clones in tumors after vaccination.</span></p>
<p><span style="font-size: 15px;">The results of these clinical trials support the mechanism of action of the personalized therapeutic cancer vaccine based on the induction of anti-tumor T cells, indicating that the personalized therapeutic cancer vaccine in combination with pembrolizumab (an anti-PD-1 monoclonal antibody) has clinical activity against advanced hepatocellular carcinoma.</span></p>
<p><span style="font-size: 15px;">Creative Biolabs offers a comprehensive suite of cancer vaccine services based on its advanced platforms for neoantigen prediction and in vitro evaluation.</span></p>
<ul>
<li><strong><span style="font-size: 15px; color: #0000ff;"><a style="color: #0000ff;" href="/vaccine/personalized-neoepitope-mrna-cancer-vaccine-platform.htm">Personalized Neoepitope mRNA Cancer Vaccine Platform</a></span></strong></li>
<li><strong><span style="font-size: 15px; color: #0000ff;"><a style="color: #0000ff;" href="/vaccine/modular-neovax-platform-for-cancer-vaccine.htm">Modular NeoVax Platform for Cancer Vaccine</a></span></strong></li>
<li><strong><span style="font-size: 15px; color: #0000ff;"><a style="color: #0000ff;" href="/vaccine/synthetic-long-peptides-slps-based-neoantigen-cancer-vaccines.htm">Synthetic Long Peptides (SLPs) Based Neoantigen Cancer Vaccines</a></span></strong></li>
<li><strong><span style="font-size: 15px; color: #0000ff;"><a style="color: #0000ff;" href="/vaccine/dendritic-cell-dcs-based-neoantigen-cancer-vaccines.htm">Dendritic Cell (DCs) Based Neoantigen Cancer Vaccines</a></span></strong></li>
<li><strong><span style="font-size: 15px; color: #0000ff;"><a style="color: #0000ff;" href="/vaccine/biomaterial-assisted-neoantigen-cancer-vaccines.htm">Biomaterial-assisted Neoantigen Cancer Vaccines</a></span></strong></li>
<li><strong><span style="font-size: 15px; color: #0000ff;"><a style="color: #0000ff;" href="/vaccine/ai-aided-analysis-platform-for-prediction-of-tumor-neoantigen.htm">AI-aided Analysis Platform for Prediction of Tumor Neoantigen</a></span></strong></li>
<li><strong><span style="font-size: 15px; color: #0000ff;"><a style="color: #0000ff;" href="/vaccine/high-efficient-neoantigen-in-vitro-evaluation-platform.htm">High-efficient Neoantigen<em data-immersive-translate-walked="d19453af-b448-426b-9bd9-033d731788c0">In Vitro</em> Evaluation Platform</a></span></strong></li>
<li><strong><span style="font-size: 15px; color: #0000ff;"><a style="color: #0000ff;" href="/vaccine/adoptive-neoantigen-activated-t-cell-transfer-therapy.htm">Adoptive Neoantigen-activated T Cell Transfer Therapy</a></span></strong></li>
<li><strong><span style="font-size: 15px; color: #0000ff;"><a style="color: #0000ff;" href="/vaccine/neotcr-t-platform-t-cells-with-tumor-neoantigen-specific-t-cell-receptors.htm">NeoTCR-T Platform- T Cells with Tumor Neoantigen-specific T Cell Receptors</a></span></strong></li>
</ul>
<p><span style="font-size: 12px;">Reference</span></p>
<ol>
<li><span style="font-size: 12px;">Yarchoan, Mark, et al. &#8220;Personalized neoantigen vaccine and pembrolizumab in advanced hepatocellular carcinoma: a phase 1/2 trial.&#8221; Nature medicine (2024): 1-10.</span></li>
</ol>
<p>&nbsp;</p>
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		<title>A Powerful Dual Anti-tumor Vaccine to Land!</title>
		<link>https://www.creative-biolabs.com/blog/vaccine/a-powerful-dual-anti-tumor-vaccine-to-land/</link>
		
		<dc:creator><![CDATA[biovaccine]]></dc:creator>
		<pubDate>Sun, 21 Apr 2024 13:18:19 +0000</pubDate>
				<category><![CDATA[Vaccine Research]]></category>
		<category><![CDATA[Exosomes Vaccine]]></category>
		<category><![CDATA[tumor vaccine]]></category>
		<category><![CDATA[vaccine design]]></category>
		<guid isPermaLink="false">https://www.creative-biolabs.com/blog/vaccine/?p=579</guid>

					<description><![CDATA[Gamma delta (γδ) T cells are a type of innate-like T cell that possess dual anti-tumor activities, capable of directly eliminating tumor cells and acting as immunostimulatory cells to enhance the body&#8217;s<a class="moretag" href="https://www.creative-biolabs.com/blog/vaccine/a-powerful-dual-anti-tumor-vaccine-to-land/">Read More...</a>]]></description>
										<content:encoded><![CDATA[<p class="MsoNormal"><span style="font-size: 15px;"><span lang="EN-US">Gamma delta (γδ) T cells are a type of innate-like T cell that possess dual anti-tumor activities, capable of directly eliminating tumor cells and acting as immunostimulatory cells to enhance the body&#8217;s anti-tumor immunity. In a recent research report titled &#8220;Tumor vaccine based on extracellular vesicles derived from γδ-T cells exerts dual antitumor activities&#8221; published in the international journal Journal of Extracellular Vesicles, scientists discovered that extracellular vesicles (exosomes) derived from </span>γδ<span lang="EN-US">-T cells not only exhibit direct anti-tumor effects but also, if developed into a <strong><span style="color: #0000ff;"><a style="color: #0000ff;" href="/vaccine/cancer-vaccines.htm">tumor vaccine</a></span></strong>, can effectively induce tumor-specific immune responses. This discovery may provide a new pathway and ideas for the development of novel cancer therapies.</span></span></p>
<p class="MsoNormal"><span lang="EN-US" style="font-size: 15px;">Extracellular vesicles are nanoscale particles secreted by cells, typically carrying a variety of substances such as lipids, proteins, and nucleic acids, and playing a crucial role in intercellular communication. They can protect vaccine components from degradation, thereby enhancing their stability and prolonging their half-life, and can enhance the uptake of antigens by antigen-presenting cells (APCs), thus potentially being explored for the development of tumor vaccines. Previous research has focused on exosomes from tumor cells (TExos) and dendritic cells (DC-Exos), but they have certain limitations in terms of safety and clinical efficacy.</span></p>
<p class="MsoNormal"><span lang="EN-US" style="font-size: 15px;">In this study, researchers focused on extracellular vesicles derived from human γδ-T cells, a rare subtype of T cells known for their direct anti-tumor activity and ability to enhance T cell responses. They found that the extracellular vesicles derived from γδ-T cells (γδ-T-Exos) exhibit dual anti-tumor activities, carrying cytotoxic and immunostimulatory molecules and capable of directly killing tumor cells and stimulating the host&#8217;s immune system. Researchers discovered that γδ-T-Exos have a certain adjuvant effect, enhancing the expression of antigen presentation and releasing pro-inflammatory molecules, thereby improving the immune system&#8217;s ability to recognize and attack tumor cells.</span></p>
<p><span style="font-size: 15px;"><img decoding="async" loading="lazy" class="aligncenter wp-image-580" src="https://www.creative-biolabs.com/blog/vaccine/wp-content/uploads/2024/04/vblog-202404-1.jpg" alt="" width="293" height="243" /></span></p>
<p><span style="font-size: 15px;">See our exosome vaccine service:</span></p>
<ul>
<li><strong><span style="font-size: 15px; color: #0000ff;"><a style="color: #0000ff;" href="/vaccine/exosome-based-therapeutic-cancer-vaccines.htm">Exosome-Based Therapeutic Cancer Vaccines</a></span></strong></li>
<li><strong><span style="font-size: 15px; color: #0000ff;"><a style="color: #0000ff;" href="/vaccine/exosome-based-vaccine-design.htm">Exosome-Based Vaccine Desig</a></span></strong></li>
</ul>
<p><span style="font-size: 15px;">By loading γδ-T-Exos onto tumor-associated antigens to develop a tumor vaccine, researchers demonstrated that it could potentially be more effective in promoting the body&#8217;s tumor-specific T-cell responses than using γδ-T-Exos alone. This <span style="color: #0000ff;"><strong><a style="color: #0000ff;" href="https://www.creative-biolabs.com/vaccine/vaccine-technology.htm">vaccine strategy</a></strong></span> also retains direct anti-tumor effects and can induce tumor cell death. Interestingly, the study findings suggest that allogeneic γδ-T-Exos (derived from different individuals) can exhibit similar preventive and therapeutic effects in mouse models as autologous γδ-T-Exos (derived from the same individual). This indicates that this method might be suitable for centralized standard production, and these vaccines also possess dual anti-tumor capabilities, effectively killing tumor cells and indirectly inducing T-cell-mediated anti-tumor immune responses, thereby controlling tumors better than existing vaccine strategies.</span></p>
<p><span style="font-size: 15px;">Researcher Tu Wenwei stated that this study first revealed the adjuvant effect of γδ-T-Exos and its ability to effectively induce tumor-specific T-cell responses when used in tumor vaccines; in various mouse models, vaccines based on γδ-T-Exos could effectively control the occurrence and progression of tumors. More importantly, vaccines based on allogeneic γδ-T-Exos show similar anti-tumor effects as those based on autologous γδ-T-Exos. Therefore, γδ-T-Exos derived from healthy donors might be used to treat patients with allogeneic tumors, greatly promoting the clinical promotion and application of new therapies.</span></p>
<p><span style="font-size: 15px;">The study results are of significant importance for cancer immunotherapy, with the adjuvant effect observed in γδ-T-Exos emphasizing their potential as cancer vaccines because they can also effectively deliver tumor antigens while having dual anti-tumor effects, surpassing the efficacy of DC-Exos-based vaccines. Furthermore, vaccines based on allogeneic γδ-T-Exos also show promise in clinical practice, as they simplify the preparation process of personalized vaccines and allow for standardized production. These findings hope to improve cancer treatment outcomes by providing a more simplified and accessible approach. Overall, this study provides a certain level of conceptual validation for the use of allogeneic γδ-T-Exos-based vaccines in cancer control.</span></p>
<p><span style="font-size: 12px;">Reference:</span></p>
<p><span style="font-size: 12px;">Wang, Xiwei, <em>et al.</em> &#8220;Tumor vaccine based on extracellular vesicles derived from γδ‐T cells exerts dual antitumor activities.&#8221; <em>Journal of Extracellular Vesicles</em> 12.9 (2023): 12360.</span></p>
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		<title>Review of Vaccine Adjuvant</title>
		<link>https://www.creative-biolabs.com/blog/vaccine/review-of-vaccine-adjuvant/</link>
		
		<dc:creator><![CDATA[biovaccine]]></dc:creator>
		<pubDate>Mon, 18 Mar 2024 07:07:48 +0000</pubDate>
				<category><![CDATA[Vaccine Review]]></category>
		<category><![CDATA[Vaccine Adjuvant]]></category>
		<guid isPermaLink="false">https://www.creative-biolabs.com/blog/vaccine/?p=572</guid>

					<description><![CDATA[Vaccination is undoubtedly one of the most remarkable health achievements in human history. In just over two centuries, vaccines have enabled us to achieve extraordinary goals, such as eradicating smallpox, eradicating polio<a class="moretag" href="https://www.creative-biolabs.com/blog/vaccine/review-of-vaccine-adjuvant/">Read More...</a>]]></description>
										<content:encoded><![CDATA[<p><span style="font-size: 15px;">Vaccination is undoubtedly one of the most remarkable health achievements in human history. In just over two centuries, vaccines have enabled us to achieve extraordinary goals, such as eradicating smallpox, eradicating polio from most parts of the world, and dramatically reducing mortality and morbidity from many infectious diseases.</span></p>
<p><span style="font-size: 15px;">Vaccination policies are the cornerstone of public health, and there is a strong emphasis on ensuring safe and effective vaccines. The effectiveness of the vaccine depends not only on the antigenic composition, but also on the adjuvants that are often used, stimulating the immune system in a more effective way. Adjuvants are components that are added to vaccines to improve the immune response to antigens. In addition, adjuvants have several benefits, such as reducing the amount of antigen and the number of vaccinations per dose of the vaccine, and in some cases, they also increase the stability of the antigenic component, extend its half-life, and indirectly improve its immunogenicity.</span></p>
<p><span style="font-size: 15px;"><a href="https://www.creative-biolabs.com/vaccine/category-antigens-1.htm"><strong><span style="color: #0000ff;">Antigens</span></strong></a> are associated with adjuvants, and they are able to induce a local pro-inflammatory response by activating the innate immune system, resulting in the recruitment of immune cells to the injection site. The antigen-adjuvant complex activates the pattern recognition receptor (PRR) pathway through pathogen-associated molecular patterns (PAMPs). This leads to the activation of innate immune cells, which produce cytokines and chemokines.</span></p>
<p><span style="font-size: 15px;">Currently, the vast majority of vaccines approved by the European Medicines Agency and the U.S. Food and Drug Administration for human use aluminum salts as adjuvants, which are the oldest adjuvants used in vaccine formulations. In order to improve the safety and efficacy of vaccines, it is necessary to increase the variety and number of new adjuvants. Advances in modern technologies, such as nanotechnology and molecular biology, have strongly facilitated the development process of adjuvant components, thereby increasing the efficacy of vaccines. A good adjuvant must be safe, effective, easy to produce, have good medicinal properties (pH, osmolality, endotoxin levels, etc.) and durability and, finally, be economically affordable. Particles, emulsions, and immunostimulants show great potential in vaccine production.</span></p>
<p><span style="font-size: 15px;"><img decoding="async" loading="lazy" class="aligncenter  wp-image-573" src="https://www.creative-biolabs.com/blog/vaccine/wp-content/uploads/2024/03/vblog-202403-1.jpg" alt="" width="387" height="186" srcset="https://www.creative-biolabs.com/blog/vaccine/wp-content/uploads/2024/03/vblog-202403-1.jpg 1080w, https://www.creative-biolabs.com/blog/vaccine/wp-content/uploads/2024/03/vblog-202403-1-300x144.jpg 300w, https://www.creative-biolabs.com/blog/vaccine/wp-content/uploads/2024/03/vblog-202403-1-1024x492.jpg 1024w, https://www.creative-biolabs.com/blog/vaccine/wp-content/uploads/2024/03/vblog-202403-1-768x369.jpg 768w" sizes="(max-width: 387px) 100vw, 387px" /></span></p>
<p style="text-align: center;"><span style="font-size: 12px;">Fig. 1 Mechanism of Action of Adjuvants.<sup>1</sup></span></p>
<p><span style="font-size: 15px;"><strong>Delivery System Adjuvant</strong></span></p>
<p><span style="font-size: 15px;"><a href="https://www.creative-biolabs.com/vaccine/category-adjuvants-5.htm"><strong><span style="color: #0000ff;">Adjuvants</span></strong></a> can be classified according to different criteria, such as their physicochemical properties, origin, and mechanism of action. One of the most talked about classification systems is based on their mechanism of action, which divides them into two broad categories: delivery system adjuvants and immune-enhancing adjuvants.</span></p>
<p><span style="font-size: 15px;">Creative Biolabs’ Adjuvant Products for Vaccine Development:</span></p>
<table>
<tbody>
<tr>
<td style="border-style: solid; border-color: #050505;" width="184"><span style="font-size: 15px; color: #0000ff;"><a style="color: #0000ff;" href="https://www.creative-biolabs.com/vaccine/l-aluminum-22.htm"><strong>Aluminum</strong></a></span></td>
<td style="border-style: solid; border-color: #050505;" width="184"><span style="font-size: 15px; color: #0000ff;"><a style="color: #0000ff;" href="https://www.creative-biolabs.com/vaccine/l-oil-adjuvant-23.htm"><strong>Oil Adjuvant</strong></a></span></td>
<td style="border-style: solid; border-color: #050505;" width="184"><span style="font-size: 15px; color: #0000ff;"><a style="color: #0000ff;" href="https://www.creative-biolabs.com/vaccine/l-saponin-40.htm"><strong>Saponin</strong></a></span></td>
</tr>
<tr>
<td style="border-style: solid; border-color: #050505;" width="184"><span style="font-size: 15px; color: #0000ff;"><a style="color: #0000ff;" href="https://www.creative-biolabs.com/vaccine/l-lipopolysaccharide-41.htm"><strong>Lipopolysaccharide</strong></a></span></td>
<td style="border-style: solid; border-color: #050505;" width="184"><span style="font-size: 15px; color: #0000ff;"><a style="color: #0000ff;" href="https://www.creative-biolabs.com/vaccine/l-cpG-21.htm"><strong>CpG</strong></a></span></td>
<td style="border-style: solid; border-color: #050505;" width="184"><span style="font-size: 15px; color: #0000ff;"><a style="color: #0000ff;" href="https://www.creative-biolabs.com/vaccine/l-prrs-agonist-24.htm"><strong>PRRs Agonist</strong></a></span></td>
</tr>
</tbody>
</table>
<p>&nbsp;</p>
<ul>
<li><span style="font-size: 15px; color: #0000ff;"><a style="color: #0000ff;" href="https://www.creative-biolabs.com/vaccine/l-aluminum-22.htm"><strong>A</strong><strong>luminum </strong><strong>S</strong><strong>alts</strong></a></span></li>
</ul>
<p><span style="font-size: 15px;">The adjuvant properties of aluminum salts were discovered in the twenties of the twentieth century, and these compounds have been used as vaccine adjuvants since 1926. As the longest-used and most frequently used adjuvant in vaccines, about one-third of currently licensed vaccines contain aluminum.</span></p>
<p><span style="font-size: 15px;">In vaccines, aluminum exists in the form of a composite polymer of crystalline aluminum hydroxide (AlH) or amorphous aluminum hydroxyl phosphate (AlP) to form aggregated nanoparticles. AlH has the appearance of needle-like nanoparticles, whereas when viewed under transmission electron microscopy, AlP appears as a reticulated. Both forms of aluminum adjuvants are generally soluble in citrate, but AlP is more soluble than AlH. The antigen is adsorbed on the surface of the adjuvant particle through electrostatic interaction and ligand exchange. Aluminum salt/antigen binding enhances antigen uptake and presentation in antigen-presenting cells (APCs). In addition, aluminum salts stimulate the activation of the NLRP3 inflammasome, leading to the production of IL-1β and IL-18, which cause local inflammation and APC recruitment.</span></p>
<p><span style="font-size: 15px;">Many vaccines use aluminum adjuvants, such as those against diphtheria and tetanus, pertussis, hepatitis B, and pneumococcal and meningococcal bacteria. In Europe, the European Pharmacopoeia sets the aluminium content in vaccines at a maximum of 1.25 mg per dose. In the United States, the Code of Federal Regulations sets the aluminum content in biological products, including vaccines, at 0.85 mg/dose. Unlike aluminum, which is predominantly in the form of soluble citrate or chloride salts in food, inorganic aluminium compounds used as adjuvants are less soluble as part of their auxiliary mode of action. Therefore, due to this poor solubility at physiological pH, the absorption rate of aluminum contained in the vaccine after intramuscular or subcutaneous injection will be very slow.</span></p>
<p><span style="font-size: 15px;">Several studies have evaluated the kinetics of aluminum after intramuscular injection. An experiment was studied based on the intramuscular injection of AlH and AlP labeled with 26Al with a total dose of 0.85 mg of aluminum. The results showed that the absorption rates of AlH and AlP were 17% and 51%, respectively, during the 28 days of the experiment. The maximum serum concentration (Cmax) of 26Al is 2 μg/L. In addition, the neurotoxicity of aluminum has been studied <em>in vitro</em>, <em>ex vivo</em>, in animal models, and in humans. Some <em>in vitro</em> studies of bacteria have shown no mutagenicity. However, some <em>in vivo</em> studies are often inconsistent and contradictory, and there may be methodological shortcomings. Therefore, to date, it has not been possible to determine whether aluminum salts used as adjuvants (at recommended doses) have toxic effects, despite the fact that they produce more or less intense oxidative stress.</span></p>
<ul>
<li><span style="font-size: 15px;"><strong>Freund&#8217;s Adjuvant</strong></span></li>
</ul>
<p><span style="font-size: 15px;">Freund&#8217;s adjuvants include both complete and incomplete Freund&#8217;s adjuvants. Both adjuvants are water-in-oil emulsions that are capable of carrying antigens and stimulating the innate immune system. Complete Freund&#8217;s adjuvant (CFA) includes in its structure heat-killed mycobacteria, which enhance the stimulation of the immune response. However, CFA is able to induce intense, long-lasting local inflammation, which can be significantly painful and may ulcerate at the injection site. Incomplete Freund&#8217;s adjuvant (IFA) does not contain mycobacteria and was used as an adjuvant in human influenza vaccines in the 1950s, where it can induce a stronger, longer-lasting antibody response than the same vaccine without adjuvant.</span></p>
<p><span style="font-size: 15px;">The adjuvant activity of IFA is based on its characteristic of being a deposit of oily antigens, from which antigens are continuously released at the injection site. This simultaneously results in an increase in the antigen half-life as well as strong local innate immune stimulation through phagocytosis, leukocyte recruitment and infiltration, and cytokines. However, the routine use of IFA in human vaccine formulations has triggered strong side effects. According to a survey conducted by the World Health Organization in 2005, 40,000 people who received immunizations from about 1 million IFA subjects experienced serious side effects (e.g., sterile abscesses).</span></p>
<ul>
<li><span style="font-size: 15px;"><strong>MF59</strong></span></li>
</ul>
<p><span style="font-size: 15px;">MF59 is a water-in-oil emulsion consisting of squalene, Span 85, and Tween 80 in 10 mM sodium citrate buffer at pH 6.5 with an average particle size of approximately 165 nm. It was the first oil-in-water emulsion approved in Italy for use in a human vaccine in 1997. Currently, it is used in the trivalent and quadrivalent (TIV and QIV) influenza vaccine, Fluad (Seqirus). Studies have shown that the presence of MF59 increases the effectiveness of the influenza vaccine in children under 2 years of age. MF59 has also been used as an adjuvant in HBV vaccines, which is able to elicit a strong immune response that is better than aluminum-induced immune responses.</span></p>
<p><span style="font-size: 15px;">Regarding the mechanism of action, MF59 has a similar effect to aluminum salts. The reservoir activity at the injection site is negligible, and studies have shown that it has a half-life of 42 hours. In contrast, MF59 has a potent ability to induce cellular and humoral immune responses, including the production of high-titer functional antibodies. The presence of MF59 stimulates local innate immune cells to secrete chemokines such as CCL4, CCL2, CCL5, and CXCL8, which in turn drive leukocyte recruitment, antigen uptake, and migration to lymph nodes by triggering adaptive immune responses. MF59 is safe and well tolerated, with millions of doses administered in more than 35 countries.</span></p>
<ul>
<li><span style="font-size: 15px;"><strong>AS03</strong></span></li>
</ul>
<p><span style="font-size: 15px;">AS03 is an oil-in-water adjuvant emulsion consisting of the surfactant polysorbate 80 and two biodegradable oils, namely squalene and DL-α-tocopherol, in phosphate buffer. This adjuvant has been used in influenza vaccines, eliciting an immune response similar to MF59, and is also used in malaria vaccines. The European Union approved the marketing of the AS03 adjuvanted vaccine Pandemrix in 2009, while the AS03 adjuvanted influenza A (H5N1) monovalent vaccine was approved by the FDA in 2013.</span></p>
<p><span style="font-size: 15px;">The antioxidant and immunostimulatory properties of α-tocopherol appear to be stronger compared to MF59. In addition, studies have shown that AS03 is able to stimulate the immune system by activating NF-κB, thereby inducing cytokine and chemokine secretion in muscles and lymph nodes and promoting the migration of innate immune cells. AS03 can also stimulate CD4+ T cell-specific immune responses, which can lead to long-lasting neutralizing antibody production and higher levels of memory B cells. AS02 is further supplemented with two powerful immunostimulants, QS-21 (a saponin extracted from Astragalus membranaceus) and 3-O-deacyl-4′-monophospholipid A (MPL), on top of AS03 to enhance its immunogenicity.</span></p>
<ul>
<li><span style="font-size: 15px;"><strong>Virus-like particles</strong></span></li>
</ul>
<p><span style="font-size: 15px;">Virus-like particles (VLPs) are icosahedral or rod-shaped nanoparticles (Å20–200 nm) composed of the outer shell of a self-assembling capsid protein, which have been used in long-term research for vaccine development. They are non-infectious particles and do not include any genetic material. VLPs are formed from an external viral shell with repetitive epitopes that are immediately recognized by the immune system as non-self, resulting in a robust immune response. In addition to these repeated structural motifs, VLPs are similar in size to viruses (typically between 20–800 nm) and are processed quickly and efficiently to produce a rapid and durable immune response, even in the absence of adjuvants.</span></p>
<p><span style="font-size: 15px;">Currently, there are two important vaccines that use virus-like particle adjuvants to induce immunity: hepatitis B and papillomavirus (HPV) vaccines. The currently used hepatitis B vaccine, a recombinant DNA vaccine containing hepatitis B surface antigen (HBsAg) in the form of VLP, is used to prevent hepatitis B infection. It is administered to infants, children, and adolescents under 15 years of age, or to people at high risk of hepatitis B infection, and has also shown good immunogenicity (95–99% efficacy) in newborns born to mothers of hepatitis B carriers.</span></p>
<p><span style="font-size: 15px;">The HPV vaccine is also a vaccine based on the VLP platform. The current 9-valent HPV vaccine protects against nine different viral genotypes, which can cause 90% of cervical cancers and 80–95% of anogenital cancers. The 9-valent HPV vaccine contains the L1 protein of nine different genotypes of HPV (6, 11, 16, 18, 31, 45, 53, 58) to form VLP and synthesize it through recombinant DNA technology.</span></p>
<ul>
<li><span style="font-size: 15px;"><strong>Virions</strong></span></li>
</ul>
<p><span style="font-size: 15px;">Virions are a vaccine platform that is structurally very similar to native viruses. Structurally, they are VLPs formed by recombinant influenza virus envelopes composed of hemagglutinin (HA), neuraminidase (NA), and phospholipids (phosphatidylethanolamine and phosphatidylcholine), which lack viral genetic material. The first use of virions in 1975 to make influenza vaccines, an adjuvanted influenza vaccine for all age groups, is effective in healthy and immunocompromised children, adults, and the elderly. It is capable of inducing B cell responses and producing specific antibodies. Virions retain the receptor-binding capacity and membrane fusion activity of viral HA, but due to the lack of viral RNA, they are unable to induce infection in cells after binding.</span></p>
<p><span style="font-size: 15px;">Virions are a perfect delivery system capable of transferring antigens into the cytoplasm of antigen-presenting cells and inducing cytotoxic T lymphocyte (CTL) responses. However, due to their weak adjuvant properties, virions are not very effective in activating APCs and facilitating cross-presentation. This intrinsic limitation can be eliminated by the addition of stronger adjuvants. For example, a novel influenza vaccine based on a virion has recently been developed, supplemented with the Toll-like receptor 4 (TLR4) ligand monophosphoryllipid a (MPLA) and the metal ion chelating lipid DOGS NTA-Ni adsorbed into the membrane. <em>In vivo</em> immunization of mice with virions with these MPLA adjuvants can induce specific CTL.</span></p>
<p><span style="font-size: 15px;">The significant advantage of virion delivery system adjuvants is their ability to adsorb antigens to their surface and lumen through hydrophobic lipid interactions. Adsorption of antigens to the surface of the fluid phospholipid bilayer of the virion stimulates interaction with host cell receptors. The FDA has approved virions as nanocarriers for human use, and they are very well tolerated and safe. In contrast to subunit vaccines, which do not respond well to viral invasion, virions are able to induce robust humoral and cellular immunity in a manner very similar to natural infection and other potent adjuvants.</span></p>
<p><span style="font-size: 15px;">To date, in addition to the two virion-based vaccines against influenza and hepatitis A mentioned above, several virion-based vaccines are being studied, including those against HIV, human papillomavirus, respiratory syncytial virus, and malaria.</span></p>
<h6><span style="font-size: 15px;"><strong>Immune Enhancer Adjuvant</strong></span></h6>
<ul>
<li><span style="font-size: 15px;"><strong>TLR1/2 agonists</strong></span></li>
</ul>
<p><span style="font-size: 15px;">Among TLR1/2 agonists, L-pampo is a potent adjuvant system consisting of Pam3Csk4 (Pam3) and polyinosinyl:polycytidylate (polyI:C). In one study, L-pampo induced the production of stronger anti-HBV antibodies than the aluminum adjuvant, and also involved cell-mediated immune responses such as increased multifunctional CD4+ T cells.</span></p>
<p><span style="font-size: 15px;">In addition, bacterial lipoproteins are the most potent ligands for TLR2 recognition. Studies have shown that synthetic lipopeptides derived from bacterial lipoproteins are strong activators of B cells and macrophages and can be used as vaccine adjuvants. Macrophage-activated lipoprotein-2 (MALP-2) from Mycoplasma fermentum is shown to activate immune cells via TLR2- and MyD88-dependent signaling pathways. In addition to MALP-2, Pam2CSK4 and Pam3CSK4 are also recognized TLR2 agonists, and they have been evaluated as therapeutics against infectious diseases such as Leishmania, malaria, and influenza.</span></p>
<ul>
<li><span style="font-size: 15px;"><strong>TLR3 agonists</strong></span></li>
</ul>
<p><span style="font-size: 15px;">TLR3 is an endosomal receptor that detects viral dsRNA, which recognizes poly(I:C) because it structurally mimics viral RNA, thereby inducing the production of type I and type III IFNs and eliciting Th1 cytokine responses. Type I IFNs produced following TLR3-poly(I:C) interactions are particularly important for the efficient activation of CD8+ T cell responses by traditional dendritic cells (cDCs). In addition, poly(I:C)-generated type I IFNs stimulate clonal expansion of T cells, increasing the ratio of effector T cells and the number of antigen-specific B cells.</span></p>
<p><span style="font-size: 15px;">Poly(I:C) has been extensively studied as a potential adjuvant. However, poly(I:C) has a toxic effect on humans. Therefore, scientists&#8217; attention has focused on derivatives of poly(I:C), such as poly(ICLC) and poly(IC12U), as well as other synthetic TLR3 agonists, such as ARNAX, IPH3102, and RGC100.</span></p>
<p><span style="font-size: 15px;">To date, several studies have used poly (ICLC) as a vaccine candidate for infectious diseases, such as Plasmodium falciparum and HIV, as well as cancer. Studies have shown that poly (ICLC) is able to elicit a stronger Th1 immune response compared to other TLR agonists such as LPS and CpG. A new TLR3 agonist with adjuvant potential is ARNAX, a TLR3-specific ligand with lower toxicity than poly(I:C). Two of the most important areas of ARNAX research are cancer immunotherapy and influenza vaccines.</span></p>
<ul>
<li><span style="font-size: 15px;"><strong>TLR4 agonists</strong></span></li>
</ul>
<p><span style="font-size: 15px;">TLR4 agonists studied as vaccine adjuvants include AS01, AS02, and AS04, all of which contain the ligand MPLA for endosomal TLR4. AS01 has been used to develop vaccines against malaria, HIV, and tuberculosis. AS01 is a combined adjuvant system consisting of two different immunostimulatory molecules, MPLA and QS-21, encapsulated in a liposomal structure. These two compounds use liposomes as carriers to reach intracellular levels through cholesterol-dependent endocytosis. Intracellularly, QS-21 causes lysosomal instability and promotes the activation of the protein kinase SYK. MPLA acts on endosome TLR4 to induce TRIF-dependent signaling pathways. AS01 activates caspase-1, thereby promoting the activation of the NLRP3 inflammasome and the release of IL-1β and IL-18 from APCs. The release of IL-18 leads to the rapid production of IFN-γ, especially in the lymph nodes, which promotes the maturation of DCs and the induction of Th1-type immune responses.</span></p>
<ul>
<li><span style="font-size: 15px;"><strong>TLR5 Agonists</strong></span></li>
</ul>
<p><span style="font-size: 15px;">TLR5 is a receptor that recognizes bacterial flagellar proteins and is expressed by several immune cells. Ligation with ligands leads to the activation of inflammatory pathways and the release of many inflammatory mediators, such as TNF-α, IL-1β, IL-6, and nitric oxide. In addition, flagellin is able to elicit Th1 and Th2 responses, whereas unlike other TLR ligands, they can only induce Th1 responses. Flagellin induces the production and release of IL-1β by activating the NLRC4 inflammasome. To date, at least three vaccines using flagellin as adjuvants are in clinical trials: two against influenza viruses and one against Yersinia pestis.</span></p>
<ul>
<li><span style="font-size: 15px;"><strong>TLR7/8 agonists</strong></span></li>
</ul>
<p><span style="font-size: 15px;">Some studies have shown that TLR7/8 agonists are able to strongly induce Th1 immune responses. Ligand binding to TLR7/8 yields high levels of type I IFN, IL-12, TNF-α, and IL-1β. In addition, TLR7/8 and TLR9 agonists are the only agonist molecules capable of activating and promoting clonal expansion of cDCs and plasmacytoid dendritic cells (pDCs), as well as mobilizing CD14+CD16+ inflammatory monocytes and CD14dimCD16+ patrol monocytes.</span></p>
<p><span style="font-size: 15px;">The most representative TLR7/8 agonists are some synthetic small molecules, such as imiquimod (R837) and requimod (R848), which belong to the class of imidazoquinolines. Imiquimod is currently approved for the treatment of genital warts, superficial basal cell carcinoma, and actinic keratosis, while raquimod has been studied for antiviral and anticancer treatments.</span></p>
<p><span style="font-size: 15px;">However, these small molecules have some inherent limitations. In particular, they can spread away from the site of administration and thus away from antigens, leading to reduced efficacy and inducing systemic side effects. The direct binding of these molecules to aluminum adjuvants has been shown to increase vaccine efficacy. In addition, the combination of synthetic polymer scaffolds, lipid polymer amphiphiles, polyethylene glycol (PEG), nanogels, alum, and various other synthetic polymers significantly increased imidazoquinoline delivery and improved DC and antigen-specific T cell maturation. In addition, previous studies using imidazoquinoline with one or more other TLR agonists (e.g., MPLA and MPLA+CpG ODN) have shown that this combination increases the innate immune response, significantly produces antigen-specific neutralizing antibodies, and improves the Th1 response. All of these innovations highlight the outstanding potential of TLR7/8 agonists as candidate adjuvants.</span></p>
<ul>
<li><span style="font-size: 15px;"><strong>TLR9 Agonists</strong></span></li>
</ul>
<p><span style="font-size: 15px;">TLR9 naturally recognizes bacterial DNA motifs represented by the unmethylated cytosine guanine phosphate (CpG) dinucleotide and drives the activation of the innate immune system through the MyD88-dependent pathway. CpG-ODNs elicit potent chemokine, cytokine, and antibody production in NK cells, B cells, and pDCs, thereby driving a strong Th1-type immune response. So far, three classes (A-C) of different classes of CpG-ODN have been developed, but only Class B molecules have been used as adjuvants in clinical trials. Type B CpG-ODN can induce the maturation of pDCs and interact directly with B cells to enhance antibody production.</span></p>
<p><span style="font-size: 15px;">The recently licensed CpG 1018, an oligonucleotide with high chemical stability and the ability to elicit an adjuvant to a Th1 immune response, is used as an adjuvant to the hepatitis B vaccine Heplisav-B. CpG 1018 in Heplisav-B increases the efficacy of the vaccine and requires only two doses of the vaccine compared to the traditional hepatitis B vaccine, which requires three doses for optimal protection. Another CpG-ODN, CpG 7909, is also being clinically evaluated and has shown encouraging results in HBV and malaria vaccination.</span></p>
<p><span style="font-size: 15px;">In addition, other next-generation TLR9 agonists are in development. MGN1703 is a small DNA molecule that includes a CG motif, but is structurally different from CPG-ODN. The MGN1703 consists of a segment of reverse complementary DNA that is double-stranded in the middle, and a single-stranded loop at both ends includes three unmethylated CG motifs, forming a dumbbell-shaped structure. MGN1703 has been tested as an adjuvant in cancer vaccines, and it has been found to be able to activate both innate and adaptive immune responses with only mild or temporary side effects.</span></p>
<p><span style="font-size: 15px;">Reference:</span></p>
<ol>
<li><span style="font-size: 15px;">Facciolà, Alessio, et al. &#8220;An overview of vaccine adjuvants: current evidence and future perspectives.&#8221; Vaccines 10.5 (2022): 819.</span></li>
</ol>
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		<item>
		<title>ACS Nano: Toll-Like Receptor 9 Agonist Boosts COVID-19 Vaccine</title>
		<link>https://www.creative-biolabs.com/blog/vaccine/acs-nano-toll-like-receptor-9-agonist-boosts-covid-19-vaccine/</link>
		
		<dc:creator><![CDATA[biovaccine]]></dc:creator>
		<pubDate>Sat, 24 Feb 2024 06:03:56 +0000</pubDate>
				<category><![CDATA[Vaccine Research]]></category>
		<category><![CDATA[COVID-19 Vaccine]]></category>
		<guid isPermaLink="false">https://www.creative-biolabs.com/blog/vaccine/?p=565</guid>

					<description><![CDATA[The development of effective vaccines for infectious diseases is one of the most successful global health interventions ever. Although subunit vaccines largely depend on the selection of antigens and adjuvants, the exposure<a class="moretag" href="https://www.creative-biolabs.com/blog/vaccine/acs-nano-toll-like-receptor-9-agonist-boosts-covid-19-vaccine/">Read More...</a>]]></description>
										<content:encoded><![CDATA[<p><span style="font-size: 15px;">The development of effective vaccines for infectious diseases is one of the most successful global health interventions ever. Although subunit vaccines largely depend on the selection of antigens and adjuvants, the exposure modes and time scales of the immune system are often overlooked. <span style="color: #0000ff;"><a style="color: #0000ff;" href="/vaccine/category-adjuvants-5.htm"><strong>Adjuvants</strong></a></span> play a crucial role in enhancing the quality and efficacy of immune responses, but unfortunately, poor control over the delivery of many adjuvants can limit their efficacy and lead to off-target toxicity. Therefore, there is an urgent need to improve adjuvant delivery technologies to improve the efficacy of adjuvants and enhance vaccine performance. The shape and size of nanoparticles mimic the structure of viruses, and so they have proven to be ideal carriers for improving antigen delivery, but exploration in adjuvant delivery is generally less common.</span></p>
<p><span style="font-size: 15px;">Recently, Professor Ben S. Ou and his team from the Department of Bioengineering at Stanford University developed a nanoparticle-based adjuvant construct to optimize CpG delivery, aiming to improve adjuvant efficacy. This research indicated that a single vaccination with CpG-NP hydrogels and soluble CpG-NP vaccines showed outstanding anti-spike protein antibody titers and broader antibody responses against immune evasion variants, reporting a simplified design of a widely implementable CpG-NP platform to increase efficacy and thus broaden and sustain the range of vaccines.</span></p>
<p><img decoding="async" loading="lazy" class="aligncenter size-full wp-image-566" src="https://www.creative-biolabs.com/blog/vaccine/wp-content/uploads/2024/02/vblog-202402-1.jpg" alt="" width="500" height="497" srcset="https://www.creative-biolabs.com/blog/vaccine/wp-content/uploads/2024/02/vblog-202402-1.jpg 500w, https://www.creative-biolabs.com/blog/vaccine/wp-content/uploads/2024/02/vblog-202402-1-300x298.jpg 300w, https://www.creative-biolabs.com/blog/vaccine/wp-content/uploads/2024/02/vblog-202402-1-150x150.jpg 150w" sizes="(max-width: 500px) 100vw, 500px" /></p>
<p style="text-align: center;"><span style="font-size: 12px;">Fig.1. Design of CpG-functionalized NPs (Ou B S, 2024)</span></p>
<p><span style="font-size: 15px;">The results show that the presentation density of CpG has a great impact on the activation of TLR9, and <em>in vitro</em> intermediate densities of CpG on the NP surface (like 30% CpG-NPs) show maximum efficacy compared to soluble CpG. When these CpG-NPs are used as adjuvants for a COVID-19 candidate vaccine using SARS-CoV-2 spike protein, they can induce a better humoral response compared to soluble <strong><span style="color: #0000ff;"><a style="color: #0000ff;" href="/vaccine/cpg.htm">CpG adjuvants</a></span></strong>. In fact, compared to soluble CpG, vaccines composed of CpG-NP adjuvants can stimulate stronger and more sustained antibody titers, stronger recognition ability of related immune phagocytic variants, a balanced Th1 to Th2 response, and stronger neutralizing antibody responses. The impact on the rheological properties of embedding CpG-NP in a PNP hydrogel can be negligible compared to standard PNP hydrogel. Despite the different physicochemical properties of CpG-NPs and SARS-CoV-2 spike protein, immobilization in a hydrogel network results in similar diffusion characteristics, enabling the sustained co-delivery of both vaccine components. The humoral response generated by a single vaccination of CpG-NP hydrogel is equivalent to the primary enhancement scheme of soluble CpG-NP vaccines.</span></p>
<p><img decoding="async" loading="lazy" class="aligncenter size-full wp-image-567" src="https://www.creative-biolabs.com/blog/vaccine/wp-content/uploads/2024/02/vblog-202402-2.jpg" alt="" width="500" height="419" srcset="https://www.creative-biolabs.com/blog/vaccine/wp-content/uploads/2024/02/vblog-202402-2.jpg 500w, https://www.creative-biolabs.com/blog/vaccine/wp-content/uploads/2024/02/vblog-202402-2-300x251.jpg 300w" sizes="(max-width: 500px) 100vw, 500px" /></p>
<p><span style="font-size: 12px;">Fig.2. Single immunization of CpG-NP hydrogel elicits neutralizing antibodies in mice (Ou B S, 2024)</span></p>
<p><span style="font-size: 15px;">In conclusion, the good performance of a single immunization with the CpG-NP hydrogel vaccine can reduce the cost of clinical vaccination, improve patient compliance, ultimately resulting in faster vaccine acceptance and increased vaccination rates, all of which are key factors in addressing rapidly developing pandemics.</span></p>
<h6>See Other Adjuvant Products:</h6>
<table style="border-style: solid; border-color: #575757;">
<tbody>
<tr>
<td style="border-style: solid; border-color: #575757;" width="277"><span style="color: #0000ff; font-size: 15px;"><a style="color: #0000ff;" href="https://www.creative-biolabs.com/vaccine/l-aluminum-22.htm"><strong>Aluminum</strong></a></span></td>
<td style="border-style: solid; border-color: #575757;" width="277"><span style="color: #0000ff; font-size: 15px;"><a style="color: #0000ff;" href="https://www.creative-biolabs.com/vaccine/l-oil-adjuvant-23.htm"><strong>Oil Adjuvant</strong></a></span></td>
</tr>
<tr>
<td style="border-style: solid; border-color: #575757;" width="277"><span style="color: #0000ff; font-size: 15px;"><a style="color: #0000ff;" href="https://www.creative-biolabs.com/vaccine/l-saponin-40.htm"><strong>Saponin</strong></a></span></td>
<td style="border-style: solid; border-color: #575757;" width="277"><span style="color: #0000ff; font-size: 15px;"><a style="color: #0000ff;" href="https://www.creative-biolabs.com/vaccine/l-lipopolysaccharide-41.htm"><strong>Lipopolysaccharide</strong></a></span></td>
</tr>
<tr>
<td style="border-style: solid; border-color: #575757;" width="277"><span style="color: #0000ff; font-size: 15px;"><a style="color: #0000ff;" href="https://www.creative-biolabs.com/vaccine/l-cpG-21.htm"><strong>CpG</strong></a></span></td>
<td style="border-style: solid; border-color: #575757;" width="277"><span style="color: #0000ff; font-size: 15px;"><a style="color: #0000ff;" href="https://www.creative-biolabs.com/vaccine/l-prrs-agonist-24.htm"><strong>PRRs Agonist</strong></a></span></td>
</tr>
</tbody>
</table>
<p><span style="font-size: 12px;">Reference:</span></p>
<p><span style="font-size: 12px;">Ou B S, Baillet J, Picece V C T M, et al. Nanoparticle-Conjugated Toll-Like Receptor 9 Agonists Improve the Potency, Durability, and Breadth of COVID-19 Vaccines[J]. ACS nano, 2024.</span></p>
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		<item>
		<title>Tumor Vaccine Enhancement Progress Revealed: What&#8217;s the Highlight?</title>
		<link>https://www.creative-biolabs.com/blog/vaccine/tumor-vaccine-enhancement-progress-revealed-whats-the-highlight/</link>
		
		<dc:creator><![CDATA[biovaccine]]></dc:creator>
		<pubDate>Sun, 28 Jan 2024 13:29:59 +0000</pubDate>
				<category><![CDATA[Vaccine Research]]></category>
		<category><![CDATA[Tumor Antigen]]></category>
		<category><![CDATA[tumor vaccine]]></category>
		<guid isPermaLink="false">https://www.creative-biolabs.com/blog/vaccine/?p=554</guid>

					<description><![CDATA[The trend in the field of cancer immunotherapy is the use of cancer vaccines. By using identified tumor antigens to stimulate the immune system, cancer vaccines can generate a specific immune response<a class="moretag" href="https://www.creative-biolabs.com/blog/vaccine/tumor-vaccine-enhancement-progress-revealed-whats-the-highlight/">Read More...</a>]]></description>
										<content:encoded><![CDATA[<p class="MsoNormal"><span lang="EN-US" style="font-size: 15px;">The trend in the field of cancer immunotherapy is the use of cancer vaccines. By using identified tumor antigens to stimulate the immune system, cancer vaccines can generate a specific immune response against tumor cells, thus causing the destruction of these cells and preventing recurrences and metastasis. Recently, a research team led by Zhao Xiao and Nie Guangjun at the National Center for Nanoscience and Technology of the Chinese Academy of Sciences proposed a strategy dubbed &#8220;peri-vaccination immune priming,&#8221; which involves enhancing the immune system through the use of bacterial nanoparticle vesicles to amplify the subsequent effects of cancer vaccines. The results of the study, titled &#8220;Bacteria-derived nanovesicles enhance tumour vaccination by trained immunity&#8221;, have been published in the journal <i>Nature Nanotechnology</i>.</span></p>
<p class="MsoNormal"><span style="font-size: 15px;"><span lang="EN-US" style="mso-fareast-font-family: 等线; mso-fareast-theme-font: minor-latin;"> </span>A healthy immune system is a prerequisite for the efficacy of cancer vaccines. However, tumor patients often experience distinct immune system dysfunction, in particular severe impairment of antigen-presenting cell function within the innate immune system, which hinders the activation of immune responses by cancer vaccines. The first focus of this study was how to intervene in immune system function during the &#8220;peri-vaccination period&#8221; to enhance the efficiency of cancer vaccines.</span></p>
<p><img decoding="async" loading="lazy" class="aligncenter size-full wp-image-560" src="https://www.creative-biolabs.com/blog/vaccine/wp-content/uploads/2024/01/v202401.jpg" alt="" width="600" height="303" srcset="https://www.creative-biolabs.com/blog/vaccine/wp-content/uploads/2024/01/v202401.jpg 600w, https://www.creative-biolabs.com/blog/vaccine/wp-content/uploads/2024/01/v202401-300x152.jpg 300w" sizes="(max-width: 600px) 100vw, 600px" /></p>
<p style="text-align: center;"><span style="font-size: 12px;">Figure 1. Schematic illustration of immune mobilization based on OMV-induced trained immunity to enhance tumour vaccinations (Liu G, 2023)</span></p>
<p><span style="font-size: 15px;">With the advancement of research in the field of immunology, scientists&#8217; understanding of the innate immune system continues to deepen. This study used a type of bacterial nanoparticle vesicle known as an <span style="color: #0000ff;"><strong><a style="color: #0000ff;" href="/vaccine/outer-membrane-vesicles-omvs-platform-for-vaccine-design.htm">outer membrane vesicle</a></strong></span> (OMV) to stimulate the body to produce a trained immune response before vaccination, thereby enhancing the function of the innate immune system. This strategy, based on nanoparticle vesicles, could fill the clinical application gap in surgical tumor antigen prediction and vaccine preparation.</span></p>
<p><span style="font-size: 15px;">The team focused their efforts on the research of nano-carriers for cancer vaccines and have developed a variety of nanoparticle carriers based on OMVs, which have effectively improved the immunogenicity of <strong><span style="color: #0000ff;"><a style="color: #0000ff;" href="/vaccine/category-antigens-1.htm">tumor antigens</a></span></strong> and the immunotherapeutic effects of vaccines. They suggested that research on cancer vaccines should not be limited to optimizing the design of the vaccine itself while ignoring the effect of the body&#8217;s immune system function on the efficacy of the vaccine.</span></p>
<p><span style="font-size: 15px;"><strong>Explore some of our tumor antigen targets:</strong></span></p>
<table style="height: 120px; width: 78.2762%; border-top-color: #050505; border-right-color: #050505; border-left-color: #050505; border-top-style: solid; border-right-style: solid; border-left-style: solid; border-bottom: 0px; margin: 0px auto;">
<tbody>
<tr>
<td style="width: 189.297px; text-align: center; vertical-align: middle; border-color: #050505; border-style: solid;"><strong><span style="font-size: 15px; color: #0000ff;"><a style="color: #0000ff;" href="https://www.creative-biolabs.com/vaccine/target-cd23-6.htm">CD23</a></span></strong></td>
<td style="width: 189.297px; text-align: center; vertical-align: middle; border-color: #050505; border-style: solid;"><strong><span style="font-size: 15px; color: #0000ff;"><a style="color: #0000ff;" href="https://www.creative-biolabs.com/vaccine/target-cd9-6.htm">CD9</a></span></strong></td>
<td style="width: 189.344px; text-align: center; vertical-align: middle; border-color: #050505; border-style: solid;"><strong><span style="font-size: 15px; color: #0000ff;"><a style="color: #0000ff;" href="https://www.creative-biolabs.com/vaccine/target-cd72-6.htm">CD72</a></span></strong></td>
</tr>
<tr>
<td style="width: 189.297px; text-align: center; vertical-align: middle; border-color: #050505; border-style: solid;"><strong><span style="font-size: 15px; color: #0000ff;"><a style="color: #0000ff;" href="https://www.creative-biolabs.com/vaccine/target-cd28-6.htm">CD28</a></span></strong></td>
<td style="width: 189.297px; text-align: center; vertical-align: middle; border-color: #050505; border-style: solid;"><strong><span style="font-size: 15px; color: #0000ff;"><a style="color: #0000ff;" href="https://www.creative-biolabs.com/vaccine/target-cd22-6.htm">CD22</a></span></strong></td>
<td style="width: 189.344px; text-align: center; vertical-align: middle; border-color: #050505; border-style: solid;"><strong><span style="font-size: 15px; color: #0000ff;"><a style="color: #0000ff;" href="https://www.creative-biolabs.com/vaccine/target-cd37-6.htm">CD37</a></span></strong></td>
</tr>
<tr>
<td style="width: 189.297px; text-align: center; vertical-align: middle; border-color: #050505; border-style: solid;"><strong><span style="font-size: 15px; color: #0000ff;"><a style="color: #0000ff;" href="https://www.creative-biolabs.com/vaccine/target-cd31-6.htm">CD31</a></span></strong></td>
<td style="width: 189.297px; text-align: center; vertical-align: middle; border-color: #050505; border-style: solid;"><strong><span style="font-size: 15px; color: #0000ff;"><a style="color: #0000ff;" href="https://www.creative-biolabs.com/vaccine/target-cd27-6.htm">CD27</a></span></strong></td>
<td style="width: 189.344px; text-align: center; vertical-align: middle; border-color: #050505; border-style: solid;"><strong><span style="font-size: 15px; color: #0000ff;"><a style="color: #0000ff;" href="https://www.creative-biolabs.com/vaccine/target-cd33-6.htm">CD33</a></span></strong></td>
</tr>
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<td style="width: 189.297px; text-align: center; vertical-align: middle; border-color: #050505; border-style: solid;"><strong><span style="font-size: 15px; color: #0000ff;"><a style="color: #0000ff;" href="https://www.creative-biolabs.com/vaccine/target-cd34-6.htm">CD34</a></span></strong></td>
<td style="width: 189.297px; text-align: center; vertical-align: middle; border-color: #050505; border-style: solid;"><strong><span style="font-size: 15px; color: #0000ff;"><a style="color: #0000ff;" href="https://www.creative-biolabs.com/vaccine/target-cd36-6.htm">CD36</a></span></strong></td>
<td style="width: 189.344px; text-align: center; vertical-align: middle; border-color: #050505; border-style: solid;"><strong><span style="font-size: 15px; color: #0000ff;"><a style="color: #0000ff;" href="https://www.creative-biolabs.com/vaccine/target-cd38-6.htm">CD38</a></span></strong></td>
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<td style="width: 189.297px; text-align: center; vertical-align: middle; border-color: #050505; border-style: solid;"><strong><span style="font-size: 15px; color: #0000ff;"><a style="color: #0000ff;" href="https://www.creative-biolabs.com/vaccine/target-cd48-6.htm">CD48</a></span></strong></td>
<td style="width: 189.297px; text-align: center; vertical-align: middle; border-color: #050505; border-style: solid;"><strong><span style="font-size: 15px; color: #0000ff;"><a style="color: #0000ff;" href="https://www.creative-biolabs.com/vaccine/target-cd4-6.htm">CD4</a></span></strong></td>
<td style="width: 189.344px; text-align: center; vertical-align: middle; border-color: #050505; border-style: solid;"><strong><span style="font-size: 15px; color: #0000ff;"><a style="color: #0000ff;" href="https://www.creative-biolabs.com/vaccine/target-c5a-6.htm">C5a</a></span></strong></td>
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<p><span style="font-size: 15px;">The study also showed that OMVs can stimulate the body to produce a high level of inflammatory factors. These factors, particularly interleukin-1β, can enter the bone marrow, affecting the differentiation process of various progenitor cells during hematopoiesis. The nano-structure of the OMVs played an important role in this process. Under nano-scale, OMVs can deliver pathogen-associated molecular pattern substances, especially lipopolysaccharides (LPS), into the cytoplasm of immune cells, activating the non-classical inflammasome signaling pathway mediated by Caspase11, lead ultimately to the secretion of Interleukin-1β and the induction of trained immunity in the body.</span></p>
<p><span style="font-size: 15px;">To sum up, the research findings have provided important evidence for the development of safe, highly gene-transfected, and targeted non-cationic mRNA delivery systems to induce durable and robust humoral and cell-mediated immunity for disease treatment.</span></p>
<p><span style="font-size: 12px;">Reference</span></p>
<p><span style="font-size: 12px;">Liu G, Ma N, Cheng K, et al. Bacteria-derived nanovesicles enhance tumour vaccination by trained immunity[J]. Nature Nanotechnology, 2023: 1-12.</span></p>
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		<title>Progress in Research on Nipah Virus Vaccine</title>
		<link>https://www.creative-biolabs.com/blog/vaccine/progress-in-research-on-nipah-virus-vaccine/</link>
		
		<dc:creator><![CDATA[biovaccine]]></dc:creator>
		<pubDate>Fri, 22 Dec 2023 04:02:23 +0000</pubDate>
				<category><![CDATA[Vaccine News]]></category>
		<category><![CDATA[Nipah Virus Vaccine]]></category>
		<guid isPermaLink="false">https://www.creative-biolabs.com/blog/vaccine/?p=547</guid>

					<description><![CDATA[Recently, researchers from the Wuhan Institute of Virology, Chinese Academy of Sciences, published a research paper titled &#8220;Both chimpanzee adenovirus-vectored and DNA vaccines induced long-term immunity against Nipah virus infection&#8221; in npj<a class="moretag" href="https://www.creative-biolabs.com/blog/vaccine/progress-in-research-on-nipah-virus-vaccine/">Read More...</a>]]></description>
										<content:encoded><![CDATA[<p><span style="font-size: 15px;">Recently, researchers from the Wuhan Institute of Virology, Chinese Academy of Sciences, published a research paper titled &#8220;Both chimpanzee adenovirus-vectored and DNA vaccines induced long-term immunity against Nipah virus infection&#8221; in npj Vaccines. The study holds the potential for further development into a candidate vaccine for the Nipah virus.</span></p>
<p><span style="font-size: 15px;">Nipah virus disease is an acute and highly fatal zoonotic infectious disease caused by Nipah virus (NiV) infection, leading to diseases in both humans and animals that affect the central nervous and respiratory systems. Patients initially exhibit flu-like symptoms such as fever, headache, dizziness, and vomiting, which can rapidly progress to severe encephalitis. Severe cases are accompanied by respiratory distress, respiratory failure, and other complications. The International Committee on Taxonomy of Viruses classifies <strong><span style="color: #0000ff;"><a style="color: #0000ff;" href="/vaccine/target-nipah-virus-9.htm">Nipah virus</a></span></strong> under the Paramyxovirinae subfamily, Henipavirus genus, as a pathogenic microorganism requiring handling in a Biosafety Level 4 (BSL-4) laboratory due to its high mortality rate, potential for outbreaks, and lack of specific treatment measures. The WHO has prioritized the Nipah virus for research due to these factors.</span></p>
<p><span style="font-size: 15px;">This study utilized the sequence-optimized NiV G as an immunogen and developed a recombinant vaccine using a defective chimpanzee adenovirus vector (AdC68-G) and a plasmid-based DNA vaccine (DNA-G). The research revealed that in the BALB/c mouse model subjected to intranasal and intramuscular immunization with AdC68-G, DNA-G prime/AdC68-G boost, a rapid and robust T-cell immune response and long-lasting neutralizing antibodies were detected. The antibodies were maintained up to 68 weeks post-immunization with no significant decline observed. Subsequent challenges using intranasal and intramuscular immunization with AdC68-G, DNA-G prime/AdC68-G boost, and intramuscular/electroporation immunization with DNA-G in a golden Syrian hamster challenge model demonstrated high titers of neutralizing antibodies against both the Nipah virus strains—NiV-Malaysia and NiV-Bangladesh. The vaccines provided complete protection against lethal infections of the two Nipah virus strains without notable weight loss, clinical symptoms, or tissue pathological damage. The viral load in the hamster&#8217;s lungs, brain, and spleen was reduced or completely cleared. This vaccine not only holds promise as a candidate vaccine for Nipah virus. Moreover, the relevant research has significant implications for the prevention and control of Nipah virus.</span></p>
<p><span style="font-size: 15px;">Creative Biolabs, leveraging its unique vaccine technology platform, can offer customized development solutions for <span style="color: #0000ff;"><strong><a style="color: #0000ff;" href="/vaccine/vaccines-for-nipah-virus.htm">Nipah virus vaccines</a></strong></span> to accelerate research progress for clients.</span></p>
<p><span style="font-size: 15px;">Our Services for the Nipah Virus Vaccine</span></p>
<ul>
<li><span style="font-size: 15px;">Construction of animal models</span></li>
<li><span style="font-size: 15px;">Prediction and modeling of T-cell epitopes</span></li>
<li><span style="font-size: 15px;">Protein expression and purification</span></li>
<li><span style="font-size: 15px;">Evaluation of immune effects</span></li>
</ul>
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